Symposium Organizers
Roger Narayan University of North Carolina and
North Carolina State University
Seeram Ramakrishna National University of Singapore
Vipul Dave Cordis Corporation, a Johnson & Johnson Company
Donglu Shi University of Cincinnati
Sungho Jin University of California-San Diego
MM1:
Session Chairs
Kevin Cooper
Mohan Edirisinghe
Monday PM, November 28, 2011
Room 103 (Hynes)
9:00 AM - MM1.1
Nanofabricated Biocompatible Hollow Cylinders as Contrast Agents for Magnetic Resonance Imaging.
Congshun Wang 1 , Xiaoning Wang 1 , Stephan Anderson 2 , Xin Zhang 1
1 Department of Mechanical Engineering, Boston University, Boston, Massachusetts, United States, 2 Department of Radiology, Boston University Medical Center, Boston, Massachusetts, United States
Show AbstractA novel nanofabrication process for biocompatible, hollow cylindrical ferromagnetic contrast agents for magnetic resonance imaging (MRI) is proposed in this paper. Unlike the existing bottom-up chemically synthesized agents, these hollow cylindrical agents, fabricated using top-down NEMS technology are geometrically distinct, yielding a local magnetic field modification resulting in distinct spectral resonance properties. The ability to tune the resonance properties based on particulate geometry and material could enable multiplexing functionality for MRI, similar to quantum dot labeling technology in optical imaging. Compared to previous works on Ni-based cylindrical-nanoshells and Fe-based double-disk particles, biocompatibility and yield issues were strongly considered in this development of a simplified NEMS fabrication process incorporating iron oxide thin films.COMSOL Multiphysics Solver was used to simulate the magnetic field distribution within and surrounding two hollow magnetic cylinders. The external magnetic field was applied along the axis of the cylinder. The simulation demonstrates a homogeneous magnetic field distribution within the cylinders, which is distinctive from the surrounding field.The fabrication methodology is as follows: (a) E-beam lithography on the PMMA coated wafer to from hole array pattern; (b) iron oxide thin film deposition by RF reactive sputtering; (c) ion milling to remove the up-facing iron oxide layer and redeposit iron oxide on the hole sidewall; (d) oxygen plasma ashing to remove all PMMA. In this process flow, the RF reactive sputtering process can yield good conformity, thereby ensuring side wall coverage. During the ion-milling, a fraction of iron oxide and silicon ejected from the substrate is redeposited on the hole sidewall; this additional redeposition also serves to make the cylinder robust with better reliability. Utilizing this process, biocompatible cylinder arrays with 20nm in thickness, 200nm in diameter, separated by a distance of 700nm were successfully fabricated.To estimate precession frequency shift of the hydrogen protons diffusing through the cylinder, the iron oxide thin film using the aforementioned RF reactive sputtering process was deposited as an unpatterned thin film on a silicon substrate for magnetic property characterization using SQUID. Based on these SQUID results, the saturation magnetic polarization of the iron oxide used for this work was found to be ~1T resulting in a predicted frequency shift of ~1MHz for the aforementioned geometric dimensions at 11.7T. The fabricated MRI contrast agent presented, to the best of our knowledge, is the first nanofabricated biocompatible hollow cylindrical agent. The novel, simplified nanofabrication process developed herein yields a robust, reproducible fabrication methodology for the further development of this new class of MRI contrast agent, which offers the potential for multiplexing as well as functional imaging capacity.
9:15 AM - MM1.2
Modeling Textural Processes during Self-Assembly of Plant-based Chiral-Nematic Liquid Crystals.
Yogesh Kumar Murugesan 1 , Alejandro Rey 1
1 Chemical Engineering, McGill University, Montreal, Quebec, Canada
Show AbstractBiological liquid crystalline polymers are found in cellulosic, chitin, and DNA based natural materials. Chiral nematic liquid crystalline orientational order is observed frozen-in in the solid state in plant cell walls and is known as a liquid crystal analogue characterized by a plywood architecture. The emergence of the plywood architecture by directed chiral nematic liquid crystal has been postulated as the mechanism hat leads to optimal cellulose fibril organization. In natural systems, tissue growth and development takes place in the presence of inclusions and second phases leaving behind characteristic defects and textures, which provide a unique testing ground for the validity of the liquid crystal self-assembly postulate. In this work, a mathematical model based on Landau–de Gennes theory of liquid crystals is used to simulate defect textures arising in the domain of self assembly due to presence of secondary phases representing plant cells, lumens and pit canals. It is shown that the obtained defect patterns observed in some plant cell walls are those expected from a truly liquid crystalline phase. The analysis reveals the nature and magnitude of the viscoelastic material parameters that lead to observed patterns in plant based helicoids through directed self-assembly. This knowledge is of significant importance for researchers in the fields of material science and tissue engineering trying to mimic the ultrastructure and mechanical properties of bone tissue using cellulosic material.
9:30 AM - **MM1.3
Nanotechnology and Its Use in Medical Devices.
Kevin Cooper 1
1 ATRM, LLC, Johnson & Johnson, Somerville, New Jersey, United States
Show AbstractAt the Advanced Technologies and Regenerative Medicine, LLC (ATRM) research and development group within the Johnson & Johnson companies, the use of nanotechnology (topographical and surface chemistry changes) to modulate physical and biological responses at the medical implant-biological interface is a growing and exciting new research area. Several unique micro and nano fabrication processes on bioabsorbable and biodurable polymers have been developed. These include plasma etching processes that have created randomly-sized surface features (5 to 200nm), and imprinting and casting processes to produce ordered patterns (200nm to 10um). Surface chemistries with various chemical groups of interest have also been developed. These unique processes have provided a platform by which ATRM can understand how nano- and micro-surfaces change a polymer’s physical and biological properties. For example, surfaces with nanoscale features can be tailored for use in medical applications that require attachment to tissue. Typically, nanopillar structures i.e. less than about one micron diameter and aspect ratio (ratio of height to diameter) greater than one were used. High aspect ratio structures have been fabricated from various bioabsorbable and biodurable polymers. Thin film tape prototypes have been tested in-vitro with tissue using shear and burst pressure models and have been shown to provide excellent tissue adhesion. Nano and micro scale features have also been shown to alter spreading of a fluid and affect surface wettability. This phenomenon can be used make a surface more wettable without altering surface chemistry. Both static and dynamic models have been used for selection of features that promote spreading on different materials. Results indicate that narrow and shallow groove features provide maximum spreading. Nanotechnology has also been utilized to investigate the effect on protein interactions. For example, evaluations of blood proteins, platelets, and whole blood interactions suggest some surfaces may be able to enhance hemostatic outcomes. Surface properties can also influence cell-biomaterial interactions, local cellular environment and cell behavior. For regenerative applications, such as blood vessel formation and artificial organs, selective cell attachment and biological function are vital. Data indicate cellular responses can be influenced by surface plasma. By customizing plasma treatments to medical devices and regenerative medicine applications, it may be possible to modify surface changes and modulate cellular responses. A review of our latest results will be presented as we explore the opportunities that nanotechnology can provide to medical applications.
10:00 AM - **MM1.4
Nano-Structured Bioactive Ceramic Layer on Metallic Materials by Growing Integration Layer(GIL) Method in Solution.
Masahiro Yoshimura 1 2 , Nobuhiro Matsushita 2
1 Materials Science and Engineering, National Cheng Kung University, Tainan Taiwan, 2 Materials and Structures Laboratory, Tokyo Institute of Technology, Yokohama Japan
Show AbstractBulk metallic materials are important materials for wide variety of applications due to their excellent mechanical, thermal and chemical properties. However they have little bio-compatibility, thus the coating/joining of biocompatible ceramic layer(s) have been considered to be essential . In the ceramic/metal coating and joining, the most difficult problem is how to overcome poor adhesion of ceramic layers by their cracking and /or peeling arising from their intrinsic brittleness. On the basis of previous researches, we proposed a novel concept and technology of “Growing Integration Layer” (GIL) between ceramics and metallic materials to improve the adhesion performance[1]. The GIL(s) can be prepared from an active component of the metallic materials by chemical and /or electrochemical reactions in a solution at low temperature of RT-200 C. They have particular features:1)Widely diffused interface(s),2)Continuously graded layers grown from the bulk(substrate),3)Low temperature process, etc. On a Ti-based Bulk Metallic Glass, TiZrCuPd, we could succeed to prepare bioactive titanate(Na-Ti-O-OH) nano-structured layer by hydrothermal-electrochemical techniques at 90-120 C[2]. They are a graded layers started from dense glassy substrate to a porous (nano-mesh) layer via partially crystallized metallic alloy and,oxide(s)/alloy mixed layer(s). Formation and characterization of those GIL layers will be presented in detail. Similarly, bioactive oxide layers could be prepared on different Ti based[3] and Zr-based[4] Bulk Metallic Glasses. (1) M. Yoshimura et al., Mater.Sci.Eng.B,148(2008)2-6. (2) N. Sugiyama, M. Yoshimura, N. Matsushita, et al., Acta Biomaterialia,5, 1367-1373(2009), Mater. Sci. Eng. B,161,31-35 (2009). (3) F-X Qin,X. M. Wang, M. Yoshimura et al., Mater. Trans.,51(3),in press (2010). (4) T. Wada, X. M. Wang, M. Yoshimura et al. J. Mater. Res.,24,2941-2948(2009).Acknowlegement : We are thankful to Prof. A. INOUE, et al., Tohoku Univ. ,Prof. K. NAKATA, et al. ,Osaka Univ. and Dr N. SUGIYAMA, et al., Tokyo Inst. Tech., in the project on Bulk Metallic Glass.
10:30 AM - MM1.5
Enhanced Dispersion Stability of Hydroxyl Apatite by Surface Modification.
Kyoungsuk Jin 1 , Hae Lin Jang 1 , Ki Tae Nam 1 , Kug Sun Hong 1
1 Materials Science and Engineering, Seoul National University, Seoul Korea (the Republic of)
Show AbstractHydroxyl-apatite (Ca10(PO4)6(OH)2, HAP) is a major inorganic compound found in hard tissue material. Because of its good biocompatibility and stability across a wide range of pH, HAP has found applications in bioimaging and drug delivery systems. For those applications, colloidal stability of nano sized bio materials in solution is important. However, due to the poor surface reactivity of HAP colloids for functionalization and a tendency for the colloids to agglomerate, widespread use in biomaterial applications have been limited. Making well-dispersed HAP nano particles in aqueous solution is also a critical factor for in-vivo application. Although there have been various attempts to disperse nano material in water through ultra-sonication, physical blending, and surface modification, this issue still remains challenge. In this work, we propose a simple yet considerably more efficient method to disperse hydroxyl-apatite nano powder in water based system through surface modification. To prepare the starting material, homogeneous nano sized HAP was synthesized in aqueous solution of pH 7 by a precipitation method. To improve dispersibility, various dispersing agents such as PVP, citric acid, and sodium citrate were functionalized on HAP surface. Surface modification was certified by measuring zeta potential and the most ideal condition for dispersion was found to be dependent on pH and temperature. Dispersion of HAP fine nano powder in water for more than 24 hours has been achieved using this method. Because the as dispersed HAP nano particles possess negatively charged functional groups, we are now examining the possibility of attaching positively charged organic dye or ligands like polythiophenes to the HAP surface for biosensor application. Furthermore, HAP can be functionalized and dispersed with glutathione to attach gold nano particle to the sulfide functional group. This development is strongly expected to open the use of HAP in applications that employ SERS for highly sensitive bio sensing in-vivo.
11:00 AM - **MM1.6
Multi-Agent Delivery Nanolayers – From Implants to Nanoparticles.
Paula Hammond 1
1 Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States
Show AbstractThe electrostatic layer-by-layer (LBL) process, involving the alternation of oppositely charged multivalent species, provides a means of constructing highly tailored ultrathin films. We have utilized this method to develop thin film coatings that can deliver proteins and biologic drugs such as growth factors at hig with highly preserved activity from surfaces and sustained release of several days to weeks; manipulation of the 2D composition of the thin films can lead to simultaneous or sequential release of different components, resulting in highly tunable multi-agent delivery (MAD) nanolayered release systems. We have investigated the use of these nanometer to micron thick films as orthopedic implant coatings, matrices for tissue engineering and wound healing, and transdermal vaccine delivery. We demonstrate that the time frame and nature of release is determined by the nanolayer architecture and degree of interdiffusion between film components. Finally, we have also used dynamic LbL layers on a nanoparticle to generate a stealth outer corona layer that ‘sheds’ at the lower pH of hypoxic tumors; this step reveals positively charged nanoparticle surfaces that are rapidly taken up by tumor cells. We translate this approach to systemic delivery of nanoparticles with the use of LbL layers that act as highly effective, and in some cases pH responsive, stabilizing layers for nanoparticles to yield long distribution times.
11:30 AM - **MM1.7
Micro- and Nano-Scale Processing of Biomedical Materials.
Mohan Edirisinghe 1
1 , University College London, London United Kingdom
Show AbstractUnconventional, novel processing methods and materials for the fast advance of biomedical engineering are essential for the clinical application of biomaterials. In this talk, pioneering work which focuses on accomplishing this goal will be discussed, taking drug-delivery and orthopaedics as the main examples.The design and development of multi-needle devices for the electrohydrodynamic generation of commercial quantities of bubbles, porous particles, capsules and threads which allow significant advances mainly in medical imaging, therapeutics and tissue engineering will be illustrated with reference to the device, process, materials and application. In this way, significant advances have been achieved, especially in the generation of stimuli-responsive nano-shell capsules for drug-delivery which allow a whole family of controlled release pathways. Template-assisted electrohydrodynamic forming of inter-locked, cell texturing bioactive deposits, primarily useful in the production of orthopaedic implants and inserts will also be demonstrated. The use of spark-plasma sintering to near net-shape Co-Cr-Mo orthopaedic alloys from micro- and nano-scale powders will be discussed; these alloys have superior properties to their cast/forged counterparts.
12:00 PM - **MM1.8
Nanostructure Processing of Advanced Biomaterials and Biosystems.
Jackie Ying 1
1 , Institute of Bioengineering and Nanotechnology, Singapore Singapore
Show AbstractNanostructured materials are of interest for a variety of applications. Through controlled synthesis in reverse microemulsions, my laboratory has achieved polymeric nanoparticles for the glucose-sensitive delivery of insulin. These stimuli-responsive materials allow for the appropriate insulin delivery to diabetic patients only when their blood sugar levels are high, without the need for external blood sugar monitoring. We have also developed apatite-polymer nanocomposite particles for the sustained, zero-order delivery of protein therapeutics. By adsorbing valuable bone morphogenetic proteins on carbonated apatite nanocrystals that are then encapsulated within biodegradable polymeric microparticles, we are able to achieve controlled release of this growth factor for the bone healing process over an extended period of time.In addition, nanostructure processing has been employed in artificial implant and tissue engineering applications. For example, nanocomposite processing has been applied to obtain orthopedic implants and bone scaffolds with superior mechanical strength and bioactivity. By combining microfabrication and nanotechnology, we have also created various microstructures in kidney-specific dimensions and shapes. These structures can be used as bioartificial renal assist microdevices, and may serve as three-dimensional templates for tissue engineering.
12:30 PM - **MM1.9
Functionalised Oxide Nanoparticles: Synthesis, Protein Adsorption and Cell Impact.
Kurosch Rezwan 1 , Timo Daberkow 2 , Fabian Meder 3 , Laura Treccani 4
1 Production Engineering, Advanced Ceramics, University of Bremen, Bremen Germany, 2 , Advanced Ceramics, University of Bremen, Bremen Germany, 3 , Advanced Ceramics, University of Bremen, Bremen Germany, 4 , Advanced Ceramics, University of Bremen, Bremen Germany
Show AbstractIn the first part of this talk is a straight-forward method for obtaining fluorescently labeled spherical metal-oxide nanoparticles with well-defined isoelectric points and narrow size distribution presented. Spherical amorphous silica nanoparticles were used as substrate material and coated with silica, alumina (Al2O3), titania (TiO2), and zirconia (ZrO2) by using sol-gel chemistry. Fluorescence labeling was achieved by directly embedding rhodamine 6G (R6G) dye into the coating matrix without affecting the isoelectric points of the metal oxide coatings. The coating was proven to be stable for at least 240 h. The synthesized and well-defined fluorescent nanoparticles can be directly used for biomedical investigations, e. g. elucidation of particle-cell interactions. Preliminary cell tests show that alumina coated silica particles reduced significantly the cell viability of human osteoblasts.In the second part of the talk the adsorption behaviour of bovine serum albumin (BSA), lysozyme (LSZ) and trypsin (TRY) onto alumina nanoparticles modified with -NH2, -COOH, -SO3H and -PO3H2 is presented. Our protein adsorption results at pH 6.9 ±0.3 identify electrostatic interaction as the dominating factor for the adsorption process at the given conditions. The spatial surface potential distribution of the protein and hydrophilic/-phobic amino acids are calculated from the protein data base file and possible adsorption modes and sites identified. The active centres of both enzymes, LSZ and TRY, are assumed to be highly accessible when adsorbed on acidic functionalised alumina. These functionalised particles with well-defined characteristics can potentially be used for directed protein adsorption or repulsion and therefore as a substrate material for further biofunctionalisation steps towards a variety of applications including protein purification systems, biocatalysts, drug carriers or biosensors.
MM2:
Session Chairs
Kurosch Rezwan
Federico Rosei
Masahiro Yoshimura
Monday PM, November 28, 2011
Room 103 (Hynes)
2:30 PM - **MM2.1
Nanoscale Properties of Implantable Biomaterials.
Federico Rosei 1
1 EMT, INRS, Varennes, Quebec, Canada
Show AbstractModifying the nanoscale structure/chemistry of materials allows to tailor and optimize their properties [1]. Our strategy rests on creating nanopatterns that act as surface cues [2,3] and affect cell behavior. We developed a chemical treatment of Ti-based materials that produces a unique nanostructured topography [4], showing that chemical oxidation is a general strategy that affects biocompatibility [5]. Our treatment generates multifunctional surfaces that promotes the growth of certain cells while inhibiting that of others, without using any growth factors. Nanostructured Ti surfaces selectively inhibit fibroblastic cell growth [4] and promote osteogenic cell activity [6] in vitro. Controling nanoscale features and functionalizing surfaces with molecular overlayers [7] will lead to a new generation of intelligent biomaterials that selectively influence cell behavior at the tissue-biomaterial interface, for example by controlling the adsorption of proteins [9]. Further enhancement of mechano-biocompatibility may be provided by coating with spider silk, whose structural/functional properties are currently being studied [10, 11].[1] F Rosei, J Phys Cond Matt 16, 1373 (2004).[2] F Cicoira, F Rosei, Surf Sci 600, 1 (2006).[3] F Variola et al, Small 5, 996 (2009).[4] F Variola et al, Biomaterials 29, 1285 (2008). [5] F Vetrone et al, Nanolett 9, 659 (2009).[6] L Richert et al, Adv. Mater. 20, 1488 (2008).[7] S Clair et al, J. Chem. Phys. 128, 144705 (2008).[8] F. Variola et al., Adv. Eng. Mater. 11, B227 (2009).[9] L. Richert, F. Variola, F. Rosei, J.D. Wuest, A. Nanci, Surf. Sci. 604, 1445 (2010).[10] C. Brown, F. Rosei, E. Traversa, S. Licoccia, Nanoscale in press (2011).[11] C Brown et al, in preparation.
3:00 PM - MM2.2
Dental Pulp Stem Cell Differentiation on Nano-Patterned Surfaces.
Chungchueh Chang 1 , Vladimir Jurukovski 1 , Zohar Bachiry 3 , John Jerome 4 , Betina Ferreira 1 , Marcia Simon 2 , Miriam Rafailovich 1
1 Materials Sceince and Engineering, SUNY at Stony Brook, Stony Brook, New York, United States, 3 , Yeshiva University High School for Girls, Holliswood, New York, United States, 4 , Suffolk County Community College, Brentwood, New York, United States, 2 Oral Biology and Pathology, SUNY at Stony Brook, Stony Brook, New York, United States
Show AbstractWe have shown that Dental Pulp Stem Cells (DPSCs) can be induced to differentiate into biomineralizing bone, simply by altering the mechanics of the substrates on which they are cultured. We, therefore, investigated the effects of DPSC function surfaces patterned with nanoscale regions wich are morphologically flat, but have different mechanical properties. The samples were prepared as follows: patterns were generated by spin-casting polymer blend films onto HF etched Si surfaces. The samples were then placed in an ion mill and the surfaces were sputtered for up to 10 minutes. The residual polymer on the surface was removed by placing the sample in an oven at 750C and the surfaces were then examined with Atomic Force Microscopy (AFM) which showed that the patterns had been imprinted onto the Si wafer. Polybutadiene was then spun-cast on these nano-patterned surfaces. Since PB is above its glass transition at ambient temperatures, the film gradually relaxes to cover the morphology of the films, forming areas where the films varied in thickness according to the underlying patterns. Since the modulus of the PB films dependend on film thickness, mechanical patterns were formed which could be imaged with the AFM in the lateral force mode. DPSCs were then plated and cultured on these nanomechanical patterned surfaces in standard media without dexamethasone. After 21 days incubation, cell morphology was imaged using confocal microscopy and the cells were found to conform to the surface patterns. The samples were also analyzed with Scanning Electron Microscopy (SEM) and Energy Dispersive X-ray analysis (EDX analysis) and all samples showed large amounts of biomineralized calcium phosphate deposits indicating that the cells were induced by the surface patterns, in the absence of dexamethosone. Hence, not only mechanics, but also mechanical patterns could induce stem cell differentiation. All research was supported in part by the NSF-MRSEC program.
3:15 PM - MM2.3
Design a Novel Nanostructured Coating for Better Osseointegration.
Lijie Grace Zhang 1 2 3 , Jose Umanzor-Alvarez 1
1 Department of Mechanical and Aerospace Engineering, The George Washington University, Washington, District of Columbia, United States, 2 , GW Institute for Biomedical Engineering (GWIBE), Washington, District of Columbia, United States, 3 , GW Institute for Nanotechnology (GWIN), Washington, District of Columbia, United States
Show AbstractWith the increasing aging of the U.S. population, there are a strikingly growing number of patients who need various orthopedic and dental implants. However, traditional orthopedic and dental implants face many complications such as infection and implant loosening which may lead to implant failures. Conventional metal implants such as titanium were chosen for orthopedic and dental applications mainly based on their excellent mechanical properties and biological inertness. Since natural bone matrix is nanometer in dimension, it is desirable to design a biologically-inspired nanostructured coating that can turn conventional inert titanium surfaces into biomimetic active interfaces, thus enhance bone cell adhesion and osseointegration. For this purpose, we designed a biomimetic nanostructured coating based on nanocrystalline hydroxyapatites (HAs) and single wall carbon nanotubes (SWCNTs). Specifically, nanocrystalline HAs with good crystallinity and biomimetic dimensions were prepared via a wet chemistry method and hydrothermal treatment; and the SWCNTs were synthesized via an arc plasma method using magnetic fields. TEM images demonstrated that the hydrothermally treated nanocrystalline HAs possessed regular rod-like nanocrystals. In addition, the length of SWCNTs can be significantly increased under external magnetic fields when compared to nanotubes produced without magnetic fields. More importantly, our results showed that the above nanomaterials can greatly promote osteoblast (bone-forming cell) functions in vitro, thus holding great promise to improve osseointegration and lengthen the lifetime of current orthopedic and dental implants.
3:30 PM - MM2.4
Engineered Nanostructured Coatings for Enhanced Protein Adhesion and Cell Growth.
Fereydoon Namavar 1 , Alexander Rubinstein 2 , Renat Sabirianov 2 , Geoffrey Thiele 3 , John Sharp 4 , Utsav Pokharel 1 , Roxanna Namavar 1 , Hani Haider 1 , Kevin Garvin 1
1 Orthopaedic Surgery and Rehabilitation, University of Nebraska Medical Center, Omaha, Nebraska, United States, 2 Physics, University of Nebraska - Omaha, Omaha, Nebraska, United States, 3 Internal Medicine – Rheumatology, University of Nebraska Medical Center, Omaha, Nebraska, United States, 4 Genetics Cell Biology & Anatomy , University of Nebraska Medical Center, Omaha, Nebraska, United States
Show Abstract Failure of osseointegration of the prosthesis prevents long-term stability, which contributes to pain, implant loosening, and infection that usually necessitates revision surgery. Cell attachment and spreading in vitro is generally mediated by adhesive proteins such as fibronectin and vitronectin. The protein adsorption combined with suitable orientation of protein and its structural changes is an important factor for biocompatibility of implants. We designed and produced pure cubic zirconia ceramic [1] coatings via an ion beam assisted deposition (IBAD) with nanostructures comparable to the size of proteins. Our ceramic coatings exhibit high hardness and a zero contact angle with serum. In contrast to Hydroxyapatite (HA), our engineered zirconia films possess excellent adhesion to all orthopaedics materials. Adhesion and proliferation experiments were performed with a bona fide mesenchymal stromal cells cell line (OMA-AD) on the nano-structured coatings and compared to Cobalt Chrome (CoCr), Titanium (Ti) and HA. Our experimental results with Alamar blue, direct cell counting, and scanning electron microscopy, clearly indicated that nano-engineered cubic zirconia is superior in supporting growth, adhesion, and proliferation. Further adhesion experiments with fibronectin (FN) from human plasma using an ELISA based technique resulted in higher FN adsorption on nanoengineered surfaces as compared to other conventional orthopedic materials. These experiments indicate a clear correlation between cell and FN adhesion. We carried out quantum mechanical calculations of the electrostatic potential for a zirconia surface of nanopyramidal shape [2] that we observed in atomic force microscopy measurements [1]. We performed Monte Carlo simulations of the initial adsorption for FN fragment (13FN3-14FN3) on the model designed nanostructured zirconium dioxide (ZrO2) surface based on non-specific inter-atom interactions. We have found that the optimal immobilization of the FN fragment on the model atomic smooth surface has a lower absolute value of adsorption energy in comparison with the model ZrO2 surface [2]. A major role in this effect plays strong, attractive electrostatic interactions between negatively charged irregular regions of the ZrO2 surface and positively charged amino acid residues of the protein fragment. These interactions are the first and most critical step of the protein adsorption on the zirconia surface. Short-range interactions further contribute to the adsorption energy and determine the final configuration of the immobilized protein on the surface. 1. F. Namavar; C.L. Cheung; R.F. Sabirianov; et. al, Nano Lett. 2008, 8,988-996. 2. R. F. Sabirianov; A. Rubinstein; F. Namavar, Phys. Chem. Chem. Phys. 2011, 13, 6597.
3:45 PM - MM2.5
Control of Bacterial Biofilm Growth on Surfaces by Nanostructural Mechanics and Geometry.
Alexander Epstein 1 2 , Allon Hochbaum 1 3 , Philseok Kim 1 2 3 , Joanna Aizenberg 1 2 3
1 School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts, United States, 2 , Wyss Institute for Biologically Inspired Engineering, Boston, Massachusetts, United States, 3 Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, United States
Show AbstractAs the dominant mode of bacterial existence, slimy surface-associated biofilms pervade natural and anthropogenic environments. Mature biofilms can be highly resistant to liquid or vapor antimicrobial attack and therefore pose persistent pathogenic threats. Surface chemistry treatments to inhibit biofilm growth have been found to only transiently affect initial attachment. In this work, we investigate the tunable effects of physical surface properties, including high-aspect-ratio (HAR) surface nanostructure arrays recently reported to induce long-range spontaneous spatial patterning of bacteria on the surface. The functional parameters and length scale regimes that control such artificial patterning for the rod-shaped pathogenic species Pseudomonas aeruginosa are elucidated through a combinatorial approach. We further report a crossover regime of biofilm growth on a HAR nanostructured surface versus the nanostructure effective stiffness. When the “softness” of the hair-like nanoarray is increased beyond a threshold, biofilm growth is inhibited as compared to a flat control surface. This is consistent with the mechanoselective adhesion of bacteria, a recently proposed mechanism previously considered unique to eukaryotic cells. Therefore by combining nanoarray-induced bacterial patterning and modulating the effective stiffness of the nanoarray—thus mimicking an extremely compliant flat surface—bacterial mechanoselective adhesion can be exploited to control and inhibit biofilm growth.
4:00 PM - MM2.6
Bacterial Adhesion and Biofilm Formation on Nanostructured Titanium Oxide Surfaces.
Ajay Singh 1 2 , Varun Vyas 1 2 , Rajendra Patil 3 , Pasquale Scopelliti 4 , Vimal Sharma 1 4 , Gero Bongiorno 4 , Alessandro Podesta 2 , Cristina Lenardi 2 4 , W. Gade 3 , Paolo Milani 2 4
1 IFOM-IEO Campus, European School of Molecular Medicine (SEMM), Milan Italy, 2 Physics, Centre for Nanostructure Materials and Interfaces (CIMAINA), , Milan Italy, 3 Department of Biotechnology, , University of Pune, Ganesh Khind, Pune India, 4 Micro and Nano Fabrication Platform, Fondazione Filarete, Pune Italy
Show AbstractBacterial infection of implants and prosthetics devices is a thorny problem because it is one of the most relevant causes of implants failure. Starting from the observation that surface nanostructure strongly influences adhesion and proliferation of many mammalian cell lines on solid substrates, an increasing interest is dedicated to the developement of new strategies for preventing bacterial adhesion and biofilm formation based on the engineering of the implant surface topography at the nanoscale. Several studies have been conducted in order to elucidate the influence of nanoscale surface morphology on prokaryotic cell attachment; however, a quantitative understanding is not yet available. Using supersonic cluster beam deposition, we produced nanostructured titania thin films with controlled and reproducible nanometre scale morphology. We characterized sample surface morphology and chemistry, we measured protein adsorption and we studied Escherichia coli and Staphylococcus aureus adhesion on nanostructured surface using quantitative methods. Our data show that bacteria adhesion on nanostructured surfaces is dependent on surface nanoscale morphology. The increase of surface roughness causes an increase of the amount of adsorbed proteins, which downplays bacterial adhesion and biofilm formation. In fact, the increase of nanoscale film roughness from 16 nm to 21 nm promotes bacterial adhesion and biofilm formation, while the further increase of roughness from 25 nm to 32 nm causes a significant less bacterial adhesion and no biofilm formation. These findings demonstrate that bacterial adhesion and biofilm formation is significantly influenced by nanoscale morphological parameters. Our results provide quantitative information about the influence of surface nanoscale morphology on bacterial adhesion and biofilm formation on titanium oxide, suggesting a novel strategy to control and to inhibit biofilm formation and bacterial adhesion on implants.
4:30 PM - **MM2.7
Spectroscopy and Simulations: Tools of Investigation for Nanobiomaterials.
Christian Bonhomme 1 , Thierry Azaies 1 , Diana Ramirez Wong 2 , Sophie Demoustier 2 , Alain Jonas 2
1 , UPMC, Paris France, 2 , UCL, Louvain la Neuve Belgium
Show AbstractIn this lecture, the latest developments in spectroscopy and ab initio calculations will be applied to the fine description of nanobiomaterials. A particular emphasis will be put on the study of complex interfaces. All the concepts will be illustrated by selected examples such as nanocargos (liposils) and functional organic nanotubes. Biomimetic derivatives will also be described.
5:00 PM - MM2.8
Photoembossing: Surface Texturing for Biomedical Application.
Nanayaa freda Hughes-Brittain 1 , Olivier Picot 1 , Carlos Sanchez 2 , John Connelly 3 , Ton Peijs 1 4 , Cees (C.W.M) Bastiaansen 4 1
1 School of Engineering and Material Science, Queen Mary University of London, London United Kingdom, 2 Departmento de Fisica de la Materia Condensada. Faculta de Ciencias, Universidad de Zaragoza, Zaragoza Spain, 3 Centre for Cutaneous Research, Queen Mary University of London, London United Kingdom, 4 Faculty of Chemistry and Chemical Engineering, Eindhoven University, Eindhoven Netherlands
Show AbstractPhotoembossing is a technique to create relief structures using a patterned U.V exposure and a thermal development step. Typically, the photo-resist consists of a polymer binder and a monomer in a 1/1 ratio which results in a solid and non-tacky material at room temperature. The photopolymer is produced into films or fibres and are exposed to U.V via a photomask or by interference pattern of two converging laser beams. Upon heating, the exposed regions begin to polymerise, generating a chemical gradient between exposed and non-illuminated region. Diffusion of monomer from the dark regions to the exposed regions generates the relief structures. Until now the selection of monomers and polymers used for photoembossing has been arbitrary. Here, new mixtures for photoembossing are presented with synthetic polymers for biomedical application. Poly (l-lactide-co-glycolide) is used with an acrylate monomer to form these surface relief structures. The textured films obtained become partially degradable due to the presence of the cross-linked acrylate network. Thiol groups are added to the photopolymer mixture to create totally degradable cross-linked networks without compromising the formation of relief structures. This processing technique also produces materials that are non-toxic and support cell adhesion and growth.
5:15 PM - MM2.9
Microscale Patterning of 3D Hydrogel Scaffolds and Microvascular Architectures.
Jennifer Lewis 1 , Robert Shepherd 2
1 Materials Research Laboratory, University of Illinois, Urbana, Illinois, United States, 2 , Harvard University, Cambridge, Massachusetts, United States
Show AbstractThe ability to pattern soft functional materials in planar and three-dimensional forms is of critical importance for several emerging applications, including tissue engineering, biomedical devices, and self-healing materials. Direct-write assembly enables one to rapidly design and fabricate soft materials in arbitrary shapes without the need for expensive tooling, dies, or lithographic masks. Recent advances in the patterning of 3D hydrogel scaffolds and microvascular architectures will be highlighted. In the first example, 3D microperiodic poly(2-hydroxyethyl methacrylate) (pHEMA) are printed, cross-linked, and rendered growth compliant for primary rat hippocampal neurons. Neuronal cells thrive on these scaffolds, forming differentiated, intricately branched networks. Confocal laser scanning microscopy reveals that both cell distribution and extent of neuronal process alignment depend upon scaffold architecture. In the second example, we demonstrate a novel route for patterning 3D hierarchical, branching microvascular networks in hydrogel matrices. These structures may find potential application as tissue engineering constructs.
5:30 PM - MM2.10
Silica Nanoneedles as a Tool for Cell Behavioral Studies.
Deepak Rajput 1 , Spencer Crowder 2 , Lino Costa 1 , Alexander Terekhov 1 , Kathleen Lansford 1 , Hak-Joon Sung 2 , William Hofmeister 1
1 Department of Materials Science and Engineering, University of Tennessee Space Institute, Tullahoma, Tennessee, United States, 2 Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee, United States
Show AbstractIn this paper, we report the fabrication and characterization of silica nanoneedles enabled by femtosecond laser micromachining. A fused silica substrate was first patterned with an amplified femtosecond laser operated in single shot mode to produce an array of high-aspect ratio and nanoscale-width holes. A negative replica of the patterned fused silica substrate was then extracted using a cellulose acetate polymer solution. The replica obtained consisted of cellulose acetate nanowires, and was then coated with a thin layer of silica by hydrolysis of silicon tetrachloride in a chemical vapor deposition process. Silica-coated replicas were employed as culture substrates for mouse embryo fibroblasts (NIH 3T3) and their interactions were observed. Compared to the silica substrate in flat areas without needles, cell attachment, spreading, and viability were reduced noticeably in the areas with nanoneedle spacing of 5 – 10 μm. These initial investigations reveal that cellular interactions with silica needles are dependent upon spacing and that this format could be useful for controlling cell-substrate interactions. The nanoneedle fabrication process and results of on going studies of cell growth will be reported.
MM3: Poster Session
Session Chairs
Vipul Dave
Sungho Jin
Roger Narayan
Seeram Ramakrishna
Donglu Shi
Tuesday AM, November 29, 2011
Exhibition Hall C (Hynes)
9:00 PM - MM3.1
Modified Surface of Gold Nanoparticles Associated with Berberine as Potential Drug Delivery Vasodilator System.
Naiara Santos 1 , Bruno Silva 2 , Lusiane Bendhack 2 , Claure Lunardi 1
1 , Faculdade de Ceilândia -FCE-UnB, Brasilia Brazil, 2 , Faculdade de Ciências Farmacêuticas de Ribeirão Preto-FCFRP-USP, Ribeirão Preto Brazil
Show AbstractGold Nanoparticles (AuNP-TG) have been synthesized and surface modified to improve the interaction to berberine (BS). Berberine is an alkaloid found in medicinal plants. It has been reported to exhibit inhibitory and antitumor effects on esophageal cancer cells (ECCs) and liver cancer cell line HepG21. It was investigated parameters such as absorption spectrrun, interaction to AuNP with BS using distribution analyses; and calculated the number of surface atoms of BS associated to AuNPs. Also, were evaluated whether the functionalization of modified AuNP-TG to berberine forming AuNP-TG-BS would modify the vascular relaxation in isolated aorta compared to berberine alone.Au(III) solution (1%) was prepared with HAuCl4, berberine chloride was from Sigma Chem.Co. and used as received. All the reagents were of analytical grade, and Ultrapure water was used as supplied. Gold nanoparticle was prepared by sodium citrate reduction method2. The surface modification of AuNP was performed adding thioglicolic acid (5 mM) to naked AuNP. The interaction of berberine with AUNP-TG was performed adding increased volumes of berberine [0 to 40µM] to AuNP-TG solution. The absorption (U-4800H), fluorescence (F-7000) spectra was recorded. NanoZetasizer equipment (Malvern Instrument) was used for recording the zeta potential and size distribution measurement. Functional studies were made in rat aortic rings pre-contracted with phenylephrine (Phe, 100nM). Cumulative concentration effect curves for the BS; AuNP-BS AuNP-TG-BS were constructed. The distribution analyses (DLS) show a uniform size with varying diameters of AuNP (60,3 ± 13 nm), AuNP-TG (116 ± 1,6 nm); AuNP-BS (1672 ±51 nm), AuNP-TG-BS (604,5 ± 19 nm) systems. The addition to BS to AuNP and AuNP-TGA were evaluated. Also was estimated the number of surface atoms, Ns2 of BS on a single AuNP and AuNPTGA.The values obtained were 3.313 and 12.700 respectively. The Uv-vis showed aggregation in AuNP-BS reinforcing the idea that AuNP were instable with BS, but when recovery with TGA were stable and can be used as a drug carrier.Financial SupportCNPq,CAPES, FAPESP, FAPDF, FINATEC.1-S. E. Skrabalak, J. Y. Chen and Y. G. Sun, Acc. Chem. Res.2008, 41, 1587.2-Turkevich, J.; Stevenson, P. C.; Hillier, J. Discuss. Faraday Soc. 1951, 11, 55-75.3-Tom, R. T.; Pradeep, T. Langmuir 2005, 21, 11896-11902.
9:00 PM - MM3.10
Replica Molding with Chitin Nanofiber Ink.
Adnan Kapetanovic 1 , Chao Zhong 1 , Yingxin Deng 1 , Marco Rolandi 1
1 , University of Washington, Tukwila, Washington, United States
Show AbstractInnovative fabrication techniques utilizing naturally abundant biomedical materials have the potential to revolutionize medical diagnosis and treatment. We present a novel method to produce chitin nanofiber-based 3D micro/nanostructures via chitin ink for use in emerging medical devices. Our method employs a simple processing procedure where bulk chitin is altered to a state where self-assembled nanofibers can be readily produced and deposited into predetermined architectures. This chitin ink is used for replica molding of multifaceted structures through airbrushing and drop casting. Optical gratings, pillars, and other geometries with features ranging from 100 nm to several microns have been demonstrated. Drop casting is advantageous because higher chitin concentrations can be used, leading to thicker and mechanically robust structures. The benefits of airbrushing are that very well defined features can be attained, but films are typically not as thick due concentration limitations. As a result these deposition methods are highly adaptable to fit the needs of the desired application and required structure. This simple yet versatile technique for patterning chitin reliably into various architectures opens the door for research into future medical applications.
9:00 PM - MM3.11
Polymeric Nanoparticles for Periodontal Antimicrobial Photodynamic Therapy.
Carla Fontana 1 , Karriann Ruggiero 2 , Song Xiaoqing 2 , Mansoor Amiji 3 , Vanderlei Bagnato 4 , Nikolaos Soukos 2
1 Department of Clinical Analysis , UNESP, Araraquara, SP Brazil, 2 Applied Molecular Photomedicine Laboratory, The Forsyth Institute, Boston, Massachusetts, United States, 3 Department of Pharmaceutical Sciences, School of Pharmacy, Bouvé College of Health Sciences, Northeastern University, Boston, Massachusetts, United States, 4 Institute of Physics of São Carlos, University of São Paulo - USP, Sao Carlos , SP, Brazil
Show AbstractObjectives: To study the photodynamic effects of poly (lactic-co-glycolic acid) (PLGA) nanoparticles loaded with the photosensitizer methylene blue (MB) on human dental plaque microorganisms in planktonic and biofilm phase. Methods: MB-loaded PLGA nanoparticles were prepared and characterized. Subgingival plaque samples were obtained from human subjects with chronic periodontitis. Suspensions of plaque microorganisms were sensitized with free methylene blue (50 μg/ml) or MB-loaded nanoparticles - (50 μg/ml equivalent to MB) for 10 minutes followed by exposure to red light of 665 nm with energy fluency of 60 J/cm2. In addition, microorganisms from the same plaque samples were cultivated anaerobically on blood agar in 96-well plates for 7 days to develop microbial biofilms. These biofilms were exposed to the same photosensitizers and light fluencies as their planktonic counterparts. After photodynamic therapy (PDT), survival fractions were calculated by counting colony-forming units (CFU). The selectivity of light for certain microorganisms was identified using whole genomic probes in the checkerboard DNA-DNA format. Results: In suspensions, PDT led to 65% and 71% reduction of CFU using free MB and nanoparticles, respectively. In biofilms, the CFU reductions were 11% and 42%. Certain microorganisms showed higher susceptibility to PDT in both suspensions and biofilms. Conclusions: The data suggest that PLGA nanoparticles encapsulated with MB had a better antimicrobial PDT action, especially on biofilm microorganisms.The research described in this paper was supported by FAPESP and PROPe Unesp Keywords: Microbiology, Bacterial, Antimicrobial agents/inhibitors, Infection, PolymersPhotodynamic therapy, polymeric nanoparticles, methylene blue, bacteria, planktonic, biofilms
9:00 PM - MM3.12
Near 100% Selectivity in Anion Exchange Reactions of Layered Zinc Hydroxy Nitrate.
Nygil Thomas 1 , Michael Rajamathi 1
1 , St. Joseph's College, Bangalore India
Show AbstractThe anionic clay, zinc hydroxy nitrate was found to selectively intercalate fluoride ions from a mixture of halide ions and chloride ions from a mixture of chloride, bromide and iodide ions. Fluoride ion was intercalated into ZHN with a selectivity of 60% from a mixture of halide ions. Chloride ion was intercalated with a selectivity of ~100% into ZHN from a mixture of chloride, bromide and iodide. The fact that bromide and iodide ions do not form the intercalated product causes 100% selectivity for chloride ions. The selectivity for chloride ions was very high (94%) even when the bromide concentration was eight times in excess. The selectivity was achieved in both concentrated and dilute salt solutions. This indicates a novel form of molecular recognition in these classes of compounds making this material attractive for separation chemistry. The trend in selectivity observed here is different from what has been observed for layered double hydroxides.
9:00 PM - MM3.13
Manipulation of Block Copolymer Microdomains by a Top-Layer.
Woon Ik Park 1 , Jae Won Jung 1 , Edwin Thomas 2 , Yeon Sik Jung 1
1 MSE, KAIST, Daejeon Korea (the Republic of), 2 Department of MSE, MIT, Boston, Massachusetts, United States
Show AbstractSelf-assembled block copolymer (BCP) microdomains have been guided or manipulated by the controls of bottom surfaces and/or side walls of lithographically defined templates. If BCP microdomains can be influenced by controlling the top surface of BCP films, we can obtain one more key to handle a BCP self-assembly process. Through crosssectional transmission electron microscopy (TEM), we found PDMS spheres are significantly deformed by depositing metal or oxide layers on top of a sphere-forming polystyrene-block-polydimethylsiloxane (PS-b-PDMS) block copolymer thin film and annealing the sample at 150 °C for two hours. The height-to-diameter ratios of the PDMS microdomains were estimated to be around 0.55 – 0.65, which is significantly smaller than those (0.75-0.85) of the BCP samples without hard top layers. These rigid top-materials provide strong constraint on underlying BCP films since their chains should be frustrated to fit into the flat interface between the hard layers and BCP films. On the other hand, if relatively soft layers such as PDMS are attached on the BCP film, their height-to-diameter ratios were identical to the cases of the BCP samples free of top layers. We also found that mixing PS homopolymers can considerably reduce the degree of deformation of the spherical microdomains and similar phenomenon is observed for other BCPs such as polystyrene-block –polyferrocenylsilanes. The deformation mechanism will be discussed based on series of experimental results and theoretical models.
9:00 PM - MM3.14
Highly Tunable Directed Self-Assembly of Block Copolymers for Nanolithography.
Woon Ik Park 1 , Jae Won Jeong 1 , Caroline Ross 2 , Yeon Sik Jung 1
1 MSE, KAIST, Daejeon Korea (the Republic of), 2 Department of MSE, MIT, Boston, Massachusetts, United States
Show AbstractAn extraordinarily large degree of geometrical tunability is demonstrated in films of a self-assembled block copolymer. A poly(2-vinylpyridine-b-dimethylsiloxane) block copolymer with highly incompatible blocks was spun-cast and treated with various solvent vapors. The degree of selective swelling in the poly(2-vinylpyridine) matrix block could be controlled over an extensive range, leading to the formation of various microdomain morphologies such as spheres, cylinders, hexagonally perforated lamellae and lamellae from the same block copolymer. The systematic control of swelling ratio and the choice of solvent vapors offer the unusual ability to control the width of very well ordered linear features within a range between 6 and 31 nm. The highly tunable cylinders were characterized by very sharp edges and straightness due to the higher χ which leads to higher interfacial energy and lower interfacial width. This methodology is particularly useful for nanolithography in that a single block copolymer film can form microdomains with a broad range of geometries and sizes without the need to change molecular weight or volume fraction.
9:00 PM - MM3.15
Immune Cell Multi-Layers Assembled Using Layer-by-Layer Processing.
Girma Endale 1 , Michael Rubner 1 , Robert Cohen 2
1 Department of Materials Science and Engineering , MIT, Cambridge, Massachusetts, United States, 2 Department of Chemical Engineering, MIT, Cambridge, Massachusetts, United States
Show AbstractA method to deposit multilayers of immune cells on substrates was developed that involved the layer-by-layer assembly of nano-scale biocompatible and biodegradable naturally occurring polymers and immune cells. We used this methodology to design three dimensional immune cell structures that maintained cell viability and functionality. This novel multilayer system of immune cells was based on the interaction between B cells and hyaluronic acid and can be used for a wide range of applications such as fundamental immunological studies, cell-based biosensors and tissue engineering. Key processing parameters that must be properly controlled to create B cell multilayers, such as solution pH and ionic strength, will be discussed.
9:00 PM - MM3.16
Nanopatterned Surfaces to Promote Osteoblasts Growth.
Emanuela Gobbi 1 2 , Vardan Galstyan 1 , Elisabetta Comini 1 , Matteo Ferroni 1 , Andrea Ponzoni 1 , Dario Zappa 1 , Giorgio Sberveglieri 1 , Sandra Sigala 3 , Guido Faglia 1
1 SENSOR Laboratory, Dept. of Chemistry and Physics for Materials Engineering , University of Brescia & IDASC-CNR, Brescia Italy, 2 Dept. of Environmental and Agricultural Sciences, University of Udine, Udine Italy, 3 Dept. of Biomedical Sciences and Biotechnologies, University of Brescia, Brescia Italy
Show AbstractNanostructured materials, which mimic the nanometer topography of the native tissues, improve biocompatible responses, and result in better tissue integration in medical implants. The creation of a desirable surface chemistry, energy, roughness and microtopography that can directly influence cellular response is extremely important for better designs of these devices. The aim of this study is to test the osteoblasts response on three nanomaterials: TiO2 nanotubes (NTs), TiO2 nanoporous (NPs) and SnO2 nanowires (NWs).SnO2 NWs were prepared on titanium discs with Vapour-Phase and Vapour-Liquid-Phase growth mechanism (Comini et al., 2009). Before the deposition, titanium discs were gold-catalyzed to control the size and dispersion of nanowires. NTs and NPs of TiO2 were obtained by electrochemical anodization method. The surface roughness, the diameter and length of tubes and the walls thickness were changed by variation of anodization parameters such as electrolyte, anodization voltage or current, anodization time and temperature. NTs of TiO2 were obtained in glycerol and ethylene glycol based electrolytes. (Galstyan et al., in press). The NPs structures were prepared on titanium sheets in aqueous solution of H2SO4, glycerol and ethylene glycol based electrolytes. Then NTs and NPs structures were annealed at 400 °C for 10 h for crystallization to the anatase phase from the initial amorphous state. The roughness of the structures and the size of pores were changed by varying the chemical composition of electrolytes and other parameters of anodization. After the production surface characterization by Scanning Electron Microscopy (SEM) and Atomic Force Microscopy (AFM) was performed.Osteoblast cultures were seeded on the different nanopatterned materials. Cell survival, adhesion and proliferation were assessed by biochemical methods and computer assisted morphology. Good cell viability was reported by MTT test. Preferential distribution of the cultured osteoblasts depending on the topographical features of the different materials surfaces was investigated by SEM analyses.ReferencesE. Comini et al. (2009) Quasi-one dimensional metal oxide semiconductor: preparation, characterization and application as chemical sensors. Progress in Materials Science 54, 1-67.V. Galstyan et al. , Vertically aligned TiO2 nanotubes on plastic substrates for flexible solar cells. Small, in press.
9:00 PM - MM3.17
Biocompatible Composite Based on Ultra-High Molecular Weight Polyethylene and Hydroxyapatite for Endoprosthesis.
Sergey Kaloshkin 1 , Alexey Maksimkin 1 , Victor Tcherdyntsev 1
1 CAMN, NUST "MISIS", Moscow Russian Federation
Show AbstractUltra-high molecular weight polyethylene (UHMWPE) is a traditional material for fabrication of acetabular cup in endoprosthesis. The major problems related to exploitation of an endoprosthesis are wear of acetabular cup, that leads to loosening and failure of the implanted joint, and osteolysis around the implant, resulting from the reaction of surrounding tissues to the wear particles. To improve wear resistance, UHMWPE can be filled with various dispersed particles, reinforced with fibers, irradiated to promote crosslinking.In order to improve the tribological properties of acetabular cup and decrease the risk of osteolysis in the surrounding tissues our work suggests using biocompatible composite based on UHMWPE and hydroxyapatite (HAP). HAP is known to have low hardness and high bioactivity. High concentration of HAP in the composite should allow significantly lowering the risk of inflammation resulting from the reaction of the wear particles from acetabular cup implant with the surrounding tissues. The major goal was to achieve maximum possible content of HAP in the composite maintaining the mechanical properties and good tribological characteristics of the material.Dispersed HAP was introduced in UHMWPE polymer matrix in solid phase using the method of mechanochemical synthesis in planetary mechanoactivator Fritsch Pulverisette 5. Thermo pressing method was used for compacting of the composite.Structural studies demonstrated the increase of the degree of crystallinity of the polymer. This can be explained by promotion of heterogenic formation of crystalline structure in UHMWPE by dispersed HAP. Based on mechanical properties, optimal concentration of HAP was determined to be around 50% by weight. The 50% content of HAP is high enough to decrease the amount of wear products of UHMWPE in friction pair. In addition, the resulting composite has higher Young’s modulus and yield strength compared to pure UHMWPE, both for stretch and compression tests. Tribological tests have shown significant reduction of friction coefficient and improvement of wear resistance, which will help increase the durability of the endoprosthesis.
9:00 PM - MM3.18
Study and Characterization of Telmisartan Controlled Release's Devices Using Cyclodextrins and Bidegradable Polymers.
Alinne Gomes 1 , Ruben Sinisterra 1 , Ivana Lula 1 , Aina Cesar 1 , Robson Santos 2
1 Chemistry, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil, 2 Biological Sciences Institute, Universidade Federal de Minas Gerais, Belo Horizonte Brazil
Show AbstractThe telmisartan/beta-cyclodextrin inclusion compound and telmisartan/poly-lactide co-glycolide acid (PLGA) controlled release’s devices have been developed for hypertension treatment. One of the important advantage is the lowest effective anti-hypertensive concentrations. Microspheres telmisartan/PLGA were did and characterized for Scanning eletronic microscopy (SEM) and release kinetics profile. Spontaneously hypertensive rats (SHR) were used for in vivo tests and telmisartan/beta-cd inclusion compound presented better results than telmisartan only. Pharmacological treatment has been shown to control and decrease the risk of cardiovascular implication. There are different drug classes to treat hypertension, including angiotensin II receptor antagonists and one of them is Telmisartan (Tel), that is highly specific for AT1 receptor. The solubility of Tel in aqueous solution is strongly pH-dependent, in the range of pH 3-9 it is only poorly soluble. One of its disadvantages of the low water solubility can be improved with the use of cyclodextrins. Cyclodextrins are cyclic oligosaccharides with internal hydrophobic cavity that can include other molecules such as medicines via non-covalent interactions, modifying their physical-chemical and biological properties, mainly solubility and bioavailability. The inclusion compound was prepared in an equimolar proportion using freeze-drying method: Telmisartan was resuspended in an aqueous beta-CD solution followed by shaking and after submitted to freeze-dried; For preparing microspheres, Telmisartan was dispersed in water and this mixture was emulsified with an oil phase containing PLGA and dichloromethane. The emulsion was stabilized in 1% polyvinyl-alcohol aqueous solution, then the solvent was evaporated and the mixture centrifuged for sedimentation of microspheres; The inclusion compound was characterized by FT-IR, XRD powder pattern diffraction and Nuclear Magnetic Resonance (NMR); The microspheres were characterized by dynamic light scattering and scanning electron microscopy (SEM);The anti-hypertensive efficacy was tested using telemetry. Results and discussion:The FT-IR, XRD and NMR results the inclusion on Tel in the β-CD and it was also observed weak interactions as van der Waals interactions and hydrogen bonds between Telmisartan and β-cyclodextrin; The 2D-NMR experiments showed a spatial interaction between Telmisartan and β-cyclodextrin;2) The microspheres showed a porous superficies and had diameters about 15 μm;3) The in vitro release kinetics study was made in buffer solution pH=2 that showed a zero order kinetics, maintaining the Telmisartan concentration constant for 200 hours;4) The anti-hypertensive efficacy was tested in vivo using telemetry and demonstrated prolonged effect of the inclusion compound Telmisartan-βCD when compared with pure Telmisartan.
9:00 PM - MM3.19
Fabrication of Three-Dimensional Micro-Environment to Study Bacterial Growth.
Adriano Otuka 1 , Carla Fontana 2 , Cleber Mendonca 1
1 , Instituto de Fisica de Sao Carlos - USP, Sao Carlos Brazil, 2 , Faculdade de Ciencias Farmaceuticas, Araraquara Brazil
Show AbstractTwo-photon absorption polymerization has been shown to be a powerful method for the fabrication of complex three-dimensional microstructures for several applications, from optical devices to biology. The nonlinear nature of the multiphoton absorption confines the polymerization to the focal volume of the laser beam, allowing the fabrication of microstructures by moving the laser focus three-dimensionally. In this work we used the two-photon polymerization to fabricate micro-environments specially designed to study bacterial growth. We have also explored the possibilities of doping the fabricated microstructures with active components, such as antibiotics and sensitizers, in order to investigate aspects of related to photodynamic therapy and drug action in the developed mivro-environments.We induced the two-photon absorption polymerization with 100-fs pulses from a Ti:sapphire laser oscillator operating at 800 nm. The structures were fabricated using an average laser power of approximately 20 mW and a 0.65-NA objective that focuses the beam into the resin. The host resin we used consists of tris(2-hydroxyethyl)isocyanurate triacrylate and ethoxylated(6) trimethyl-lolpropane triacrylate. The sample was positioned in the axial z-direction using a motorized stage, and the laser beam was scanned in the resin x-y-direction with a set of galvanic mirrors. After fabrication, the unpolymerized resin is washed away with ethanol and dried at room temperature. We fabricated microstructures with dimensions on the order of tenths to hundreds of micrometers, which were characterized by scanning electron micrographs. Such microstructures were then used as platforms to investigate the growth of E.coli, which was carried out using optical transmission, fluorescent and confocal microscopy. The approach employed here is a promising alternative for the fabrication of tailor-made scaffolds to study bacterial growth, opening new venues for advanced drug delivery systems.
9:00 PM - MM3.20
Biocompatibility Studies of Plasma-Polymerized PEG Film In Vitro and In Vivo.
Changrok Choi 1 , Donggeun Jung 2 , Dong Hyun Jo 3 , Sang Yun Han 1 , Dae Won Moon 1 , Jeong Hun Kim 3 , Tae Geol Lee 1
1 Center for Nano-Bio Convergence, Korea Research Institute of Standards and Science, Daejeon Korea (the Republic of), 2 Department of Physics, Sungkyunkwan University, Suwon Korea (the Republic of), 3 Department of Ophthalmology, Seoul National University College of Medicine, Seoul Korea (the Republic of)
Show AbstractBio-compatible materials, which have low immune response and blood compatibility, have been widely used in biomedical fields such as medicine, medical devices, tissue engineering and biomaterials science. Among many bio-compatible materials, polyethylene glycol (PEG) is one of the most popular materials because it has hydrophilic and non-biofouling properties. In this work, we deposited the plasma-polymerized polyethylene glycol (PP-PEG) thin film onto various substrates by using the capacitively coupled plasma chemical vapor deposition (CCP-CVD) method and PEG monomer (MW=200) as a precursor. PP-PEG thin film has not only highly chemical similarity with PEG polymer but also has good insolubility in DI water or organic solvent. To evaluate the biocompatibility of PP-PEG film in vitro, we deposited it on various substrates such as glass, ITO glass, polyethylene terephthalate (PET), polyethylene (PE) and then analyzed each surface taken from human serum adsorption test and whole blood flow test by using MALDI-TOF, XPS and SEM. Compared to control surfaces (i.e., PP-PEG uncoated surfaces), there were no blood proteins adsorbed on PP-PEG coated surfaces after human serum adsorption test. In addition, there was no thrombus on PP-PEG coated surfaces after in vitro whole blood flow test. For in vivo applications of PP-PEG film, its biocompatibility was studied by implanting into subcutaneous space of both groin areas of C57BL/6J mice polyethylene (PE) that had been coated with or without PP-PEG, and was investigated through histological examination as well as the degree of any adhesions of the implanted PP-PEG coated PE film after 1 week and 4 weeks post-implantation. Our results confirmed a good in vivo biocompatibility. Based on these biocompatibility studies of our PP-PEG thin films, we are optimistic that our PP-PEG film can be used for various in vitro and in vivo bio-applications.
9:00 PM - MM3.22
Guiding Directional Cell Migration with Microarray Amplification of Natural Directional Persistence.
Kyu-Shik Mun 1 , Carlos Co 1 , Chia-Chi Ho 1
1 Chemical and Materials Engineering, University of Cincinnati, Cincinnati, Ohio, United States
Show AbstractIn vivo, different cell types assemble in specific patterns to form functional organs. Reproducing this process in vitro by designing scaffold materials to direct cells precisely to the right locations at the right time is important for the next generation of biomaterials. We have discovered recently a new principle, Microarray Amplification of Natural Directional Persistence (MANDIP), to guide the long-range directional migration of attached mammalian cells. Amplification of directional persistence occurs through the asymmetric positioning of individual micro-sized adhesive islands and restriction of lamellipodia attachment, and thus migration, to one preset direction. Free from gradients and external fields, MANDIP arrays are highly scalable and can operate in parallel to direct large volumes of cellular traffic on complex paths analogous to traffic signs and roadways used to regulate automobile traffic.Here, we present MANDIP design strategies to promote lamellipodia extension and attachment, accelerate cytoskeletal remodeling, and maximize migration velocity. For example, increasing the angle between islands accelerates the rate of cell displacement because the linear displacement resulting from each hop is increased. The hopping frequency also increases because of the reduced cytoskeletal rearrangement necessary for cells to move between islands. However, with increasing angle, the odds of extended lamellipodia attaching to either neighboring islands become progressively similar thereby reducing directional control. Studies with NIH 3T3 fibroblasts, human microvascular endothelial cells, and human epidermal keratinocytes (HEK) suggest that the design of the MANDIP pattern is largely independent of cell type.
9:00 PM - MM3.23
Validation of Processing Parameters for Plasma Enhanced Chemical Vapor Deposition Using Nano Thermal Analysis.
Khoren Sahagian 1 , Mikki Larner 2 , Stephen Kaplan 2
1 , Anasys Instruments, Santa Barbara, California, United States, 2 , Plasma Technology Systems, Belmont, California, United States
Show AbstractPlasma Enhanced Chemical Vapor Deposition (PECVD) is a rapidly growing technology providing unique thin films on a wide variety of substrates. As a plasma process the characteristics of the deposition product is influenced by the plasma parameters. In this study an unsaturated fluoroalkene, hexafluoropropylene, is deposited via PECVD on commercially available glass slides. The effect, due to the variation of the processing parameters, on the coating properties is qualified by nano thermal analysis (nanoTA). NanoTA makes use of a micro-fabricated silicon probe with an integrated heating element. This probe can be used in place of a standard Atomic Force Microscope (AFM) probe to scan a sample and generate an image of the topography. The probe then has the novel utility of probing softening points at select locations by increasing the temperature of the probe until the surface softens due to the local temperature increasing above a transition temperature. This allows nanoscale measurements of the transition temperature on the surface of the sample with good correlation to conventional bulk techniques.
9:00 PM - MM3.24
Characterization of Silver Doped Hdyroxyapatite Prepared by EDTA Chelate Decomposition Method.
Kubra Celik 1 , Celaletdin Ergun 2 , Huseyin Kizil 1
1 Materials Science and Engineering, Istanbul Technical University, Istanbul Turkey, 2 Mechanical Engineering, Istanbul Technical University, Istanbul Turkey
Show AbstractAmong calcium phosphates, hydroxyapatite, (HA), (Ca10(PO)6(OH)2) is known to be the major constituent (69%) of the bones. It is also an attractive material for hard tissue implants [1]. As a bioceramic, particular attention has been given to HA due to its bioresorbability [2]. It was found that changes in powder formulation and processing routes have a significant influence on the characteristic properties of hydroxyapatite [3]. With its lattice arrangement, HA can be considered a loosely packed hexagonal structure. As provided by the high flexibility of the apatite structure a great variety of cationic and anionic species can be substituted into HA structure specifically considered as an effective method to modify the properties of HA [4]. The substitution of Ag+ (1.28 Å) into the HA structure ions takes place for Ca2+ (0.99 Å) preferentially in the Ca(1) site of HA, and this leads to an increase in the lattice parameters linearly with the amount of silver added in the range of atomic ratio Ag/(Ag+Ca) between 0 and 0.055.The present study shows the preparation steps of Ag-doped hydroxyapatite (Ag-HA) via EDTA chelate decomposition method and their characterization by SEM, AFM, and antimicrobial sensitivity tests. The aim is to precipitate Ag-doped hydroxyapatite powders from aqueous solutions of the Ca(NO3)2, (NH4)H2PO4 with EDTA chelate solutions at a ratio of Ca/P:1,667.Increasing Ag ratio the sinterability of HA increased because of the new unexpected phase formation of NaCaPO4 on the HA structure which stated from XRD results of samples. When annealing temperature is greater than 800°C, a small amount of the rhenanite (NaCaPO4) phase appears, indicating the incorporation of Na+ in the synthetic HA coming from EDTA chelate (C10H14N2Na2O8.2H2O) [10].This processing resulted in the formation of NaCaPO4 (rhenanite) interphase on hydroxyapatite. The NaCaPO4 exhibits also high biocompatibility and bioactivity. Results show that various microstructurally controlled hydroxyapatite-based composites with NaCaPO4 interphase can be prepared as potentially improved reliable and high biocompatibile material. Moreover, it significantly enhances sinterability of hydroxyapatite at 1100° C without formation of any undesired phases, such as tricalcium phosphate (TCP) or CaO which decrease the stability of HA[10].To understand antibacterial properties of the structure, the antibacterial sensitivity has been tested with E.Coli Gram- negative bacteria. The radius of area which encloses the samples shows the region of non-bacterial environment. The radius increases with Ag ratio. With increasing Ag ratio the resistance to bacteria activity increases. The XRD results show that the Ag took place as Ag2O phase on the structure.
9:00 PM - MM3.25
Sensing of Oligopeptides Using Gold Nanorods for Surface-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry.
Yasuro Niidome 1 2 , Yuki Nakamura 1 , Naotoshi Nakashima 1 2 3
1 Dept. Applied Chemistry, Kyushu University, Fukuoka Japan, 2 , I2CNER, Fukuoka Japan, 3 , CREST, Tokyo Japan
Show AbstractGold nanorods were fixed on an ITO plate and used for Surface-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (SALDI-MS) of oligopeptides (angiotensin I). The longitudinal surface plasmon bands of the gold nanorods responded to the 10-10 M angiotensin solution that was cast on the ITO plate. The SALDI-MS measurements had an ultra-high sensitivity to the angiotensin on the ITO plate. A very small surface density (5 × 10-19 mol/cm2) of angiotensin could be detected at m/z = 1297 with a good signal/noise ratio (S/N = 11). The ITO plate, which was modified with gold nanorods, was found to be effective in collecting angiotensin molecules adjacent to the gold nanorods, and the SALDI processes that were induced by the photoabsorption of the gold nanorods efficiently contributed the desorption and ionization of the angiotensin.
9:00 PM - MM3.26
Imidazole-Conjugated Chitosan for Gene Therapy.
Bingyang Shi 1 , Sheng Dai 1 , Jingxiu Bi 1
1 , University of Adelaide, Adelaide, South Australia, Australia
Show AbstractChitosan using as the vector in gene therapy shows good biocompatibility and has been increasingly proposed as safer alternatives to viral vector, but poor solubility and low transfection efficiency limit its end-use applications. A novel chitosan derivative, imidazole-chitosan (ICS) were synthesized and characterized, for the purpose of gene delivery. The transmittance of the ICS solution at different pH values suggested that the water solubility of ICS had been improved. Gel electrophoresis results showed strong DNA binding ability of the ICS and the plasmid DNA is protected from Dnase digestion. The resulting ICS/DNA complexes did not induce remarkable cytotoxicity against HEK293T cell lines. Cell transfection results was evaluated by delivering pEGFP plasmid DNA in HEK293T cells, and demonstrated its higher gene transfer efficiency than chitosan, PEI (polyethylenimines) and Lipofectamine 2000. Therefore, the ICS is recommended as one of the promising candidate as the vector in gene therapy due to its good biodegradability, enhanced solubility in physiological pH, strong gene binding ability, low cytotoxicity, and competitive high cell transfection efficiency.
9:00 PM - MM3.4
Creating Surface-Modified Porous Polymers with Superhydrophilic-Superhydrophobic Micropatterns for High-Density Cell Microarrays and Cell Patterning.
Erica Ueda 1 , Florian Geyer 1 2 , Urban Liebel 1 , Pavel Levkin 1 2
1 Institute of Toxicology & Genetics, Karlsruhe Institute of Technology, Eggenstein-Leopoldshafen Germany, 2 Department of Applied Physical Chemistry, Heidelberg University, Heidelberg Germany
Show AbstractThe majority of current cell microarray technologies are based on culturing a lawn of cells on a substrate printed with spots of a chemical library. Although this enables cell screening in a high throughput and miniaturized manner, these cell microarrays require large spot-to-spot distances to reduce both cross-contamination of the spotted solutions and cell migration between the spots. Furthermore, the large spot-to-spot distances limit the achievable spot density of cell microarrays. We present a method to overcome these limitations by polymerizing a thin, nanoporous layer of superhydrophilic polymer, poly(2-hydroxyethyl methacrylate-co-ethylene dimethacrylate), on a substrate and using the surface modification technique of UV-initiated photografting and a photomask to pattern superhydrophobic barriers. This method creates densely packed superhydrophilic microspots separated by narrow superhydrophobic barriers and enables up to 50,000 spots on an area of 11 x 7 cm^2, the size of a microtiter plate. Precise control over the size and geometry of the superhydrophilic-superhydrophobic patterns is achievable based on the photomask design. We observed cell proliferation and migration on patterned substrates using several commonly used cell lines. The cells preferentially adhered and proliferated in the superhydrophilic microspots. In addition, the superhydrophobic barriers proved highly efficient at preventing cell migration between the microspots and provided watertight barriers to contain solution printed in a single microspot. To test the application of our cell microarray, we printed plasmid DNA containing a fluorescent reporter and transfection reagents on our substrate and reversely transfected HEK 293 cells. We observed efficient reporter expression in the HEK 293 cells. An additional advantage of our patterned substrates is the transparency of the nanoporous superhydrophilic polymer, which makes inverted microscopy possible. Our technology demonstrates a simple and quick method for fabricating cell microarrays and cell patterning substrates and provides an affordable and convenient biological tool.
9:00 PM - MM3.5
In Situ Guidance of Individual Neuronal Processes by Wet Femtosecond-Laser Processing of Self-Assembled Monolayers.
Hideaki Yamamoto 1 2 , Kazunori Okano 3 4 , Takanori Demura 5 , Yoichiroh Hosokawa 4 , Takashi Tanii 2 5 , Shun Nakamura 1
1 Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology School of Engineering, Koganei-shi, Tokyo, Japan, 2 Nanotechnology Research Center, Waseda University Institute for Nanoscience and Nanotechnology, Shinjuku-ku, Tokyo, Japan, 3 Kansei Fukushi Research Center, Tohoku Fukushi University, Sendai-shi, Miyagi, Japan, 4 , Nara Institute of Science and Technology Graduate School of Materials Science, Ikoma-shi, Nara, Japan, 5 Department of Electronic and Photonic Systems, Waseda University School of Fundamental Science and Engineering, Shinjuku-ku, Tokyo, Japan
Show AbstractIn-situ guidance of neuronal processes (neurites) is demonstrated by applying wet femtosecond (fs)-laser processing to an organosilane self-assembled monolayer (SAM) template. The SAM template for arraying primary neurons was prepared by patterning with electron-beam lithography aminosilane and octadecylsilane SAMs on a glass substrate, which form cytophilic and cytophobic regions, respectively. Cytophilic pattern consisted of an array of 15 μm-circles each of which is protruding four short lines (1 μm in width and 22.5 μm in length) in mutually perpendicular direction. Primary neuron was obtained from embryonic chick forebrain and was cultured on the SAM template for two days. The neurons adhered selectively on the circular pattern, frequently one cell per circle, and elongated neurites along the lines. Focused fs-laser beam (120 fs, 800 nm, 0.5 mW @1 kHz) was then scanned on the cytophobic octadecylsilane region in order to extend the line available for neurite elongation. 24 h after the laser scanning, we confirmed that neurites elongated precisely along the laser scanning line. This guidance was accomplished by multiphoton laser ablation of octadecylsilane and subsequent adsorption of cell adhesion molecule, laminin, onto the ablated region. The in-situ guidance technique presented here will enables us to design neuronal networks in vitro with controlled polarity, cell type, and synaptic site.
9:00 PM - MM3.6
Transdermal Insulin Delivery Using a Solid-in-Oil Dispersion of Gold Nanorods.
Dakrong Pissuwan 1 , Keisuke Nose 1 , Yoshiro Tahara 1 , Masahiro Goto 1 2 , Yoshiki Katayama 1 2 3 , Takuro Niidome 1 2 3
1 Department of Applied Chemistry, Faculty of Engineering, Kyushu University, Fukuoka, Fukuoka, Japan, 2 Center for Future Chemistry, Kyushu University, Fukuoka, Fukuoka, Japan, 3 International Research Center for Molecular Systems, Kyushu University, Fukuoka, Fukuoka, Japan
Show AbstractTransdermal delivery is an attractive route for protein/drug delivery as it reduces the systematic toxicity that may occur with oral or intravenous administrations. For effective transdermal delivery, the protein/drug must be capable to pass through the skin barrier and attain the specific target. Recently, we constructed an enhanced transdermal protein delivery system, that is, solid-in-oil (S/O) dispersions containing ovalbumin and gold nanorods were prepared. The greater enhancement effect on protein delivery was observed after treatment mouse skins with the S/O dispersion of gold nanorods, irradiated by near infrared light and further incubated for 12 h (Small 2, 215-220, 2011). This implies that stratum corneum layer was partly ablated by a photothermal effect of gold nanorods that had been applied to the skin.
In this study, we tried to deliver insulin using this transdermal protein delivery system. A S/O dispersion containing FITC-labelled insulin and the gold nanorods was prepared, then, permeation of insulin into mouse skins was examined using a Franz diffusion cell system. A Significantly larger amount of insulin penetrated through the skin than that of the control case without the gold nanorods or the light irradiation. We next examined a reduction of blood glucose level in mice. Streptozotocin was injected to mice to induce high blood glucose level, and then the mice were treated with the S/O dispersion system, following with near infrared light irradiation. A significant reduction of the glucose level in diabetic mice was observed after treatment of the S/O dispersion system and the light irradiation, indicating that photothermal effect of the goldnanorods enhance permeability of stratum corneum layer of the skin, then insulin was effectively transferred into the blood circulation.
This approach controlled by light irradiation will be functional tools for transdermal protein delivery.
9:00 PM - MM3.7
Hydrothermal Synthesis of Bioinert Oxide Film on Pure Ti: In Vitro and In Vitro Studies.
Masato Ueda 1 4 , Masahiko Ikeda 1 , Richard Langford 2 , Jeremy Skepper 3 , Ruth Cameron 4 , Serena Best 4
1 Chemistry and Materials Engineering, Kansai University, Suita Japan, 4 Materials Science & Metallurgy, University of Cambridge, Cambridge United Kingdom, 2 The Cavendish Laboratory, University of Cambridge, Cambridge United Kingdom, 3 Physiology, Development and Neuroscience, University of Cambridge, Cambridge United Kingdom
Show AbstractTitanium and its alloys have been used widely as biomaterials for orthopaedic implants because of their excellent mechanical properties and biocompatibility. These alloys have also been employed in bone plates/ screws, and these are often designed to be removed after recovery. Bone is known to bond to the surface of Ti alloys. This can lead to re-fracture of newly repaired bone during operations to remove the implants, however bone does not bond to Zr-based alloys. The inhibition of bone conduction on the surface of Zr-based alloys is thought to be due to the presence of a thin layer of zirconia (ZrO2) on the surface. The purpose of the present study was to synthesise bioinert films, including ZrO2 on pure Ti surfaces. Apatite (HAp) formation on the films in Hanks’ solution and in-vivo bone conduction in the tibiae of rats were also investigated.Commercial purity Ti was chemically treated with aqueous 5 M H2O2/ 0.1 M HNO3 at 353 K for 20 min. The disks were hydrothermally treated with aqueous 100 mM ZrOCl2/ 5 M NH3/ x C6H8O7 (citric acid, x= 0-600 mM) in a Teflon-lined autoclave at 453 K for 12 h. The specimens were immersed in Hanks’ solution. After being soaked for different periods of time, the surfaces were observed by SEM. Implant specimens, 2 mm in diameter and 5 mm in height, were implanted into tibiae of eight-week-old rats. After two weeks, the peripheral sections were extracted. Tissues embedded in polymer were cut and polished and the contact ratio of bone and implant was measured by using optical microscopy. In the hydrothermal treatment with aqueous ZrOCl2/ NH3, the surface product was anatase-type TiO2. On the other hand, when citric acid was added the surface of Ti was covered homogeneously with a TiO2–ZrO2 composite film though the amount of ZrO2 was very small. Some of the Zr(OH)4 sol in the solution is thought to have dissolved into the solution by coordinate bonding with citric acid carboxyl groups, leading to precipitation of ZrO2 in the TiO2 or on its surface. The relative volume fraction of ZrO2 to TiO2 in the surface products showed a maximum at x= 400 mM. TiO2 is known to dissolve sparingly in alkaline solutions. The inclusion of ZrO2 into the film requires the presence of citric acid, but the addition of excess acid seems to suppress the dissolution/ re-precipitation of TiO2. HAp began to form on the non-modified Ti and TiO2 surfaces after 6 days and 2 days immersion in Hank’s solution, respectively. On the surfaces treated with the solutions of x= 400 and 600, the presence of precipitates was confirmed after 6 and 8 days, respectively. The HAp formation was supressed on the surfaces even though the main constituent of the surfaces was TiO2 which is known to promote the deposition of HAp. This suppression of HAp formation is probably due to the small amount of ZrO2 in the TiO2.The present TiO2-ZrO2 surface also showed significantly lower bone-implant contact ratio in cortical bone compared with TiO2.
9:00 PM - MM3.8
Fabrication of Biodegradable Polymer/HAp Composites by Microwave Irradiation.
Saori Kadota 1 , Masahiro Yoshizawa-Fujita 1 , Yuko Takeoka 1 , Mamoru Aizawa 2 , Masahiro Rikukawa 1
1 Department of Materials and Life Sciences, Faculty of Science and Technology, Sophia University, Chiyoda-ku, Tokyo Japan, 2 Department of Applied Chemistry, Meiji University, Kawasaki-shi, Kanagawa Japan
Show AbstractRecently, composites of biodegradable polymers and hydroxyapatite (HAp) ceramics have been studied to apply artificially-grafting materials. These composites are expected to improve the flexibility and mechanical properties of HAp by mixing flexible biodegradable polymers. Polylactones and polycarbonates, which have biodegradability and flexibility, can be synthesized by using various catalysts such as organometallic compounds and lipases. By using lipases as catalysts, toxic effects of catalyst residues on human body can be avoided. However, enzymatic polymerizations of polylactones and polycarbonates require long reaction time. In this study, we attempted to polymerize biodegradable polymers in porous HAp ceramics using microwave irradiation in order to obtain biodegradable polymer/HAp composites in short reaction times. ω-Pentadecalactone (PDL) was successfully polymerized for 2-8 h at 100 °C in microporous-HAp (p-HAp) using microwave irradiation. The pore size and porosity of p-HAp were about 1 µm and 40 %, respectively. All the PPDL/p-HAp composites had higher bending strengths than pure p-HAp, which were close to that of natural bone. Elastic modulus of PPDL/p-HAp was the same as that of pure HAp. To promote oseteoconductivity as artificial bone materials, macro porous-HAp (mp-HAp), which had interconnected macro and micro porous, was also fabricated by microwave irradiation. The pore size of macro and micro pores of mp-HAp were about 100 µm and 1 µm, and, the porosity of mp-HAp was 70 %. Using mp-HAp, PPDL/mp-HAp composites were synthesized by microwave irradiation. All the PPDL/mp-HAp composites showed high flexibility in contrast to pure p-HAp. On the other hand, the bending strengths of PPDL/mp-HAp composites were lower than those of PPDL/p-HAp composites. The crystallinities of PPDL polymerized in p-HAp and mp-HAp ceramics were determined by differential scanning calorimeter. The crystallinities of PPDL (in mp-HAp) and PPDL (in p-HAp) polymerized at 100 °C for 6 h were 1.1 % and 9.2 %, respectively. Mws of PPDL (in mp-HAp) and PPDL (in p-HAp) polymerized at 100 °C for 2-8 h were in the range of 54,000-98,000 and 29,000-47,000, respectively. From these results, pore size of HAp ceramics effected the polymerization of PPDL.In order to improve mechanical strength of PPDL/mp-HAp, we also fabricated polylactone/polycarbonate/mp-HAp composites by microwave irradiation. PPDL and poly(trimethylenecarbonate) (PTMC) copolymers were synthesized enzymatically in mp-HAp pellets under microwave irradiation. The relationship between the copolymer composition of PPDL and PTMC, and mechanical properties of the composites were investigated.
Symposium Organizers
Roger Narayan University of North Carolina and
North Carolina State University
Seeram Ramakrishna National University of Singapore
Vipul Dave Cordis Corporation, a Johnson & Johnson Company
Donglu Shi University of Cincinnati
Sungho Jin University of California-San Diego
MM4:
Session Chairs
Julie Gough
Kalpana Katti
Tuesday AM, November 29, 2011
Room 103 (Hynes)
9:15 AM - MM4.2
Supersonic Cluster Beam Implantation: A Novel Approach for Producing Metal-Polymer Nanocomposites Based Microcircuits for Stretchable Biomedical Devices.
Paolo Milani 1 2 , Gabriele Corbelli 1 2 , Cristian Ghisleri 1 2 , Luca Ravagnan 2
1 CIMAINA & Physics Department, Università degli Studi di Milano, Milano Italy, 2 , WISE s.r.l., Milano Italy
Show AbstractThe interest for micro- and nano-manufacturing of polymeric materials is continuously increasing driven by different fields such as polymer-based BioMEMS, stretchable electronics, bioelectronics, conformable sensors and actuators. The need for polymer-based micro-devices requires the integration of micrometric electrodes, circuits and interconnections on soft and compliant polymeric substrates. Unfortunately, the standard approaches used for producing such structures have many drawbacks in terms of layer adhesion, electrical functionality under stretching, attainable lateral resolution, sample heating and biocompatibility of the obtained materials. Recently we developed a new method for polymer metallization: the Supersonic Cluster Beam Implantation (SCBI) of neutral metal nanoparticles (or clusters, with size of about 5 nm) in a polymer substrate. The nanoparticles are produced in the form of a supersonic beam by a Pulsed Microplasma Cluster Source (PMCS) [1] and are implanted at RT in the polymer substrate forming a metal-polymer nanocomposite layer [2, 3]. This process avoids both sample heating and sample charging, enabling the metallization of ultracompliant soft polymeric materials. Here we present the application of SCBI for the fabrication of a biocompatible elastomer-based nanocomposite material made by gold nanoparticles implanted in a polydimethylsiloxane (PDMS) matrix. At odd with electrodes obtained by standard approaches, the ones produced by SCBI are able to withstand thousands of uni-axial stretching cycles (over 50000 at 40% strain), showing an improvement (i.e. the decrease) of the electrical resistance at maximum strain as the number of stretching cycles increases, and only a very small increase of the rest resistance (i.e. at 0% strain). Furthermore, electrical conduction is preserved also during extreme stretching, so that open circuiting is observed only when the PDMS substrate mechanically breaks. Biocompatibility tests indicate that neuronal cells adhesion and vitality improve on the nanocomposite, proving the high biocompatibility of this novel material. Finally, we demonstrated the possibility to use SCBI to pattern compliant electrodes with micrometric resolution through standard stencil mask patterning. These results indicate that SCBI can be considered a promising tool for the fabrication of complex microelectronic circuits and interconnects on stretchable and compliant supports, preserving the electrical performances of the devices even after extensive cycles of stretching. The devices can be efficiently fabricated on biocompatible platforms, and therefore are suitable for the production of the next generation polymer-based implantable biomedical devices.[1] K. Wegner, et al., J. Phys. D: Appl. Phys. 39, R439 (2006). [2] L. Ravagnan, et al., J. Phys. D: Appl. Phys. 42, 082002 (2009).[3] M. Marelli, et al., J. Micromech. Microeng. 21 045013 (2011).
9:30 AM - MM4.3
A Chitin Nanofiber Ink: Replica Molding, Microcontact Printing, and Inkjet Printing.
Marco Rolandi 1
1 Materials Science and Engineering, University of Washington, Seattle, Washington, United States
Show AbstractThe ability to easily manufacture and manipulate biomaterials is key to the development of biocompatible medical devices. Harsh fabrication techniques derived from the semiconductor industry are often incompatible with biomaterials. Furthermore, these techniques do not take advantage of the natural self-assembly properties that can be exploited to create nanostructures. Chitin has attracted increased attention in biocompatible device fabrication. Chitin has excellent thermal stability, mechanical strength, biodegradability, and anti-microbial properties. However, chitin water insolubility has limited chitin nanofibers to electro spinning with difficult nano- and microstructure fabrication. Here, we present a facile approach to chitin nano- and microstructures composed of self-assembled nanofibers. We have developed a hexafluoro 2-propanol (HFIP) based “chitin nanofiber ink”, which self-assembles into ultrafine (3nm) nanofibers upon drying. The chitin nanofiber ink is exploited to fabricate 2-D and 3-D structures via replica molding, microcontact printing, and inkjet printing. Examples include circles, squares, pillars, and optical gratings with features ranging from sub-100 nm to several microns. Cell growth and proliferation studies on these nanofiber structures will be discussed.
9:45 AM - MM4.4
Electrospun Aligned Nanofibers Guiding Cardiomyocyte Orientation for Cardiac Tissue Engineering.
Dan Kai 1 , Molamma Prabhakaran 2 , Seeram Ramakrishna 3
1 NUS Graduate School for Integrative Sciences & Engineering, National university of Singapore, Singapore Singapore, 2 Nanoscience and Nanotechnology Initiative, National University of Singapore, Singapore Singapore, 3 Department of Mechanical Engineering, National University of Singapore, Singapore Singapore
Show AbstractBackground: Myocardial infarction (MI) is one of the most common heart disease which results in cardiac dysfunctioning, death of cardiomyocytes (CM) and ultimate heart failure. Cardiac tissue engineering (TE) is one of the most promising strategies to reconstruct infarcted myocardium, and the major challenge in cardiac TE is to produce a bioactive substrate with aligned fibrillar structure to mimick the extracelluar matrix (ECM) which provides essential guidance for cell orientation, survival and function. Materials and Methods: Random and aligned poly(ε-caprolactone) (PCL) and PCL/gelatin nanofibers were fabricated by electrospinning process. PCL was dissolved in chloroform/methanol at a weight ratio of 18% by overnight stirring, while PCL and gelatin was dissolved in HFP to obtain a 7 wt% solution concentration at a weight ratio of 50:50, by stirring for 24 h. Morphology, chemical and mechanical properties of PCL/gelatin nanofibrous scaffolds were measured by scanning electron microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR), contact angle and tensile measurements, and the in vitro biodegradability of the different nanofibrous scaffolds were evaluated too. Isolated rabbit CMs were cultured on the random and aligned electrospun scaffolds to assess scaffold behaviour towards the cell proliferation, structure and function.Results: The average fiber diameters of PCL and PCL/gelatin nanofibers were 430 ± 108 nm and 269 ± 33 nm, respectively. Blending PCL with gelatin resulted in the amine and carboxylic functional groups distributions on the electrospun PCL/gelatin nanofibers. The hydrophilicity of PCL/gelatin nanofibrous scaffolds were improved, and yielded better mechanical and biodegradation properties compared to PCL nanofibers. The cell proliferation assay indicated that aligned PCL/gelatin scaffold promoted cell attachment and proliferation compared to the other scaffolds. SEM images revealed that the hydrophilic and aligned nanofibrous architecture of PCL/gelatin scaffold guided the orientation, elongation and anisotropic growth of CMs. Immunostaining analysis by confocal microscopy further confirmed that the CMs on PCL/gelatin nanofibers expressed higher levels of cardiac specific proteins, such as α-actinin, troponin-T and connexin-43, and aligned nanofibrous structure resulted in the elongation of cell nuclear and the orientation of protein cytoskeleton, similar to those observed in heart architecture. Conclusion: Electrospun aligned PCL/gelatin nanofibrous scaffold proved to accelerate the proliferation of CM and oriented along the fiber length and are promising substrates suitable for the regeneration of infarcted myocardium and other cardiac defects.
10:00 AM - MM4.5
Nanofibrous Scaffolds for Regeneration: From Porous Foam to Self-assembled Hollow Microspheres
Peter Ma 1 2 3
1 Biologic and Materials Sciences, University of Michigan, Ann Arbor, Michigan, United States, 2 Materials Science and Engineering, University of Michigan, Ann Arbor, Michigan, United States, 3 Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, United States
Show AbstractRegenerative medicine aims to develop biological repair of lost or diseased tissues. Scaffolding materials provide three-dimensional environments for cells and serve as templates for tissue regeneration. Our lab develops biomimetic polymer scaffolds that recapitulate certain advantageous features of the natural extracellular-matrices (ECM) and impart engineering design to facilitate tissue regeneration. Novel phase separation techniques have been developed in our laboratory to create biodegradable ECM-mimicking nanofibrous scaffolds. Porous network design and computer assisted body-part shape creation allow for patient specific scaffold fabrication. These scaffolds have been shown to advantageously support various stem cells to regenerate bone and cartilage tissues in a predetermined shape. To repair complexly shaped tissue defects, an injectable cell carrier is desirable to achieve accurate fit and to minimize surgical intervention. To incorporate the ECM-mimicking nanofibrous feature into an injectable scaffold format, we have recently developed star-shaped biodegradable polymers that can self-assemble into nanofibrous hollow microspheres as novel injectable cell carriers. The nanofibrous hollow microspheres have been shown to efficiently accommodate cells and enhance cartilage regeneration over control microspheres. The nanofibrous hollow microspheres also support a significantly larger amount and higher quality cartilage regeneration over the chondrocytes alone group and a chondrocyte-encapsulated PEG hydrogel group. In a critical-size rabbit osteochondral defect repair model, the nanofibrous hollow microspheres/chondrocytes group achieved substantially better cartilage repair and integration than the chondrocytes alone group that simulates the clinically available autologous chondrocyte implantation (ACI) procedure. These results demonstrate that the nanofibrous scaffolds both in a porous foam format or an injectable hollow microsphere format advantageously support bone and cartilage regeneration.
10:15 AM - **MM4.6
Using Cellulose Nanowhiskers to Guide Myoblast Orientation and Fusion for Skeletal Muscle Tissue Engineering.
Julie Gough 1 , James Dugan 1 , Stephen Eichhorn 1
1 Materials Science Centre, University of Manchester, Manchester United Kingdom
Show AbstractIt is known that both microscale and nanoscale substrate features can affect cell behaviour and aligned features can cause contact guidance in cells. This may be of benefit for engineering tissues whose in vivo architecture consists of distinct aligned fibrous structures such as ligament and skeletal muscle. Here we report that oriented cellulose nanowhiskers (CNWs) of less than 10nm in height direct myoblast alignment, differentiation and fusion to produce highly aligned myotubes. The CNWs were prepared from the tunicates Halocynthia roretzi and Ascidiella aspersa by partial hydrolysis with sulphuric acid to produce a stable aqueous suspension of whisker-like nanoparticles with a net anionic charge. These were then spin coated onto glass coated in the cationic polymer, polyallylamine hydrochloride. Atomic force microscopy, fluorescence/confocal microscopy and image analysis were used to characterise and quantify the size and orientation of the CNWs and the orientation and differentiation of the myoblasts. Depending on spin speed a high degree of orientation of the CNWs was achieved. The two different sources of CNWs yielded different sized whiskers (10-15nm or 5-6 nm diameter), both of which were able to cause striking myoblast alignment during their proliferative phase. Myoblast differentiation and fusion to form long multinucleated myotubes occurred with the expression of proteins characteristic of differentiated myotubes. This study shows that features of only 5-6nm are capable of controlling myoblast alignment and subsequent fusion into aligned myotubes.
11:00 AM - **MM4.7
Nanoclays in Bone Tissue Engineering Scaffolds.
Avinash Ambre 1 , Dinesh Katti 1 , Kalpana Katti 1
1 Civil Engineering, North Dakota State University, Fargo, North Dakota, United States
Show AbstractDeveloping scaffolds with adequate mechanical properties that can temporarily restore the function of a damaged bone tissue and at the same time provide proper environment for the growth of a regenerating bone tissue is one of the challenges in bone tissue engineering. The ability of montmorillonite (MMT) clay to improve the mechanical properties in case of polymer-clay nanocomposites (PCNs) is well-known and can be extended for the development of polymer composite scaffolds based on MMT clay. Based on the understanding gained through the “altered phase theory” developed by our group, MMT clay modified with unnatural amino acid (valeric acid) was used for the fabrication of polymer/clay composite scaffolds. The choice of unnatural amino acids as modifiers for MMT clay was based on their functional groups, longer backbone chain length compared to the natural amino acids, and our simulations studies on intercalation of aminoacids in clay galleries. Assessing the behavior of cells (e.g. proliferation and differentiation) on new materials to be used for bone tissue engineering applications is one of the vital aspects of bone tissue engineering that further guides the design of scaffolds. Therefore, the biocompatibility of the MMT clay modified with unnatural amino acid was assessed through cell culture experiments and was further used for the preparation of biopolymer/modified clay scaffolds. Cell proliferation assay performed on biopolymer/modified clay scaffolds using osteoblasts indicated that the scaffolds supported osteoblast growth and it was also found that these scaffolds satisfied the requirements of porosity. In addition human mesenchymal stem cells were observed to show adequate properties of cell attachment, growth, proliferation and differentiation. Scaffolds of this novel nanocomposite system are fabricated using a variety of polymers and biopolymer systems (polycapralactone, chitosan, polygalactouronic acid). We also report a novel biomineralization procedure developed that uses the clay galleries with amino acids as mineralization sites for hydroxyapatite to enhance the osteoconductive properties of the scaffolds. We also report studies conducted in a bioreactor of the growth of hMSCs. Based on several biocompatibility assays, mechanical tests and also extensive spectroscopic investigations the nanoclays –polymer system appears to present as a viable biomaterial system.
11:30 AM - **MM4.8
Novel Electrospun Bicomponent Scaffolds for Bone Tissue Engineering: Fabrication, Characterization and Sustained Release of Growth Factor.
Chong Wang 1 , Min Wang 1 , Xiao-Yan Yuan 2
1 Department of Mechanical Engineering, The University of Hong Kong, Hong Kong Hong Kong, 2 School of Materials Science and Engineering, Tianjin University, Tianjin China
Show AbstractMany techniques have been investigated to form different 3D scaffolds for bone tissue engineering. Electrospinning has attracted great attention in the tissue engineering field because it is a simple and versatile technique for fiber production and electrospun fibrous scaffolds mimic the extracellular matrix of body tissues and can elicit excellent cell response. Our previous studies have demonstrated: (1) Calcium phosphate (Ca-P) nanoparticles could be incorporated into electrospun fibers and these osteoconductive nanocomposite fibers promote osteoblastic cell proliferation and differentiation better than pure polymer fibers; (2) The controlled release of recombinant human bone morphogenetic protein (rhBMP-2) from scaffolds produced by selective laser sintering provides the scaffolds with desired osteoinductivity. Our recent work has shown that growth factors such as rhBMP-2 could be successfully incorporated in polymer fibers through emulsion electrospinning. In the current investigation, multifunctional bicomponent fibrous scaffolds were fabricated for bone tissue engineering using our established dual-source dual-power electrospinning technique. In the novel bicomponent scaffolds, one component was electrospun Ca-P/PLGA nanocomposite fibers and the other component was emulsion electrospun D,L-PLA nanofibers containing rhBMP-2. Through electrospinning optimization, both types of fibers were evenly distributed in bicomponent scaffolds. For achieving balanced osteoconductivity and osteoinductivity for the scaffolds, the mass ratio of rhBMP-2/D,L-PLA fibers to Ca-P/PLGA fibers in bicomponent scaffolds could be controlled in the dual-source dual-power electrospinning process. Using various techniques, the structure and properties of bicomponent scaffolds were characterized. The in vitro release profile of rhBMP-2 as well as degradation behaviour of scaffolds was studied. To further modulate the release behaviour of rhBMP-2, different amounts of polyethylene glycol (PEG) with a molecular weight of 6,000 were used to formulate emulsions for the formation of the emulsion electrospun component. Scaffolds with the modified emulsion electrospun component exhibited better sustained release of rhBMP-2.
12:00 PM - **MM4.9
Simulations Driven Biomaterials Design for Bone Tissue Engineering.
Dinesh Katti 1 , Kalpana Katti 1
1 Civil Engineering, North Dakota State University, Fargo, North Dakota, United States
Show Abstract We have recently evaluated nanoclays as potential components of scaffolds for bone tissue engineering. Here we report molecular modeling studies of interactions and energetics of various components of the scaffold materials: nanoclays (montmorillonite), clay modifiers (amino acids), polymers and hydroxyapatite. This study represents a fundamental approach to the design of biomaterials that could allow for better predictability and tailoring of properties of biomaterials. This work builds upon the simulations based design approach for nano-clay based nanocomposites and the underlying ‘altered phase theory’ of polymer clay nanocomposites developed by our group that elucidates the enhancement of properties in nano-clay based composites. The molecular interactions between constituents of nano-clay based composites play a key role on the mechanical properties of the composite. Parameters for the individual components of the multiphase system are obtained using ab initio studies and incorporated into molecular models. Specifically we report studies on valeric acid modified nanoclays with insitu mineralized hydroxyapatite. Clay gallery separation and particle sizes are obtained from transmission electron microscopy and x-ray diffraction. Molecular models of real material system are constructed using a combination of experimental and simulations. The molecular interactions between the nanocomposite constituents are evaluated using molecular dynamics simulations. Maps of interaction energies between constituents are developed. These maps, along with the altered phase theory provide an insight into how the various moieties of the nanocomposite would impact the properties of the nanocomposite. This simulations driven approach provides a unique route for design of new nanocomposites for bone tissue engineering scaffolds.
12:30 PM - **MM4.10
Surface-Patterned Microgels to Control Biomaterials-Associated Infection.
Matthew Libera 1
1 Department of Chemical Engineering and Materials Science, Stevens Institute of Technology, Hoboken, New Jersey, United States
Show AbstractThe surfaces of many implantable biomedical devices are carefully engineered to stimulate desirable mammalian cell adhesion, spreading, and proliferation, but these are simultaneously adhesive to most bacteria and thus are susceptible to microbial colonization. The biomaterials-associated infection that can result is now a critical clinical problem. When an implanted device such as a hip or knee prosthesis becomes colonized by a bacterial biofilm, multiple interventions are required to remove the implant, resolve the infection, and replace the prosthetic. The consequences to both the patient and the health-care system are serious. Over the past decade there has been increasing effort to create surface coatings that resist bacterial colonization, but these can interfere with the adhesion and proliferation of tissue cells associated with healing. We have identified a mechanism to create a surface that can simultaneously promote healing while reducing the probability of infection using submicron-sized, non-adhesive microgels patterned on an otherwise cell-adhesive surface. We use electron-beam lithography to convert thin films of poly(ethylene glycol) [PEG] into microgels patterned at controllable inter-gel spacings (~0.5 – 5 microns) on an otherwise cell-adhesive surface. Quantitative force measurements between a staphylococcus and surfaces with laterally modulated cell adhesiveness show that the adhesion strength decreases significantly at inter-gel spacings comparable to bacterial dimensions (~ 1 micron). Time-resolved flow-chamber measurements show that the microbial deposition rate dramatically decreases at these same inter-gel spacings. Importantly, the adhesion and spreading of osteoblast-like cells is preserved. Despite the presence of the non-adhesive microgels, the surface still presents a significant fraction of cell-adhesive area and, in contrast to staphylococci that have highly crosslinked and relatively rigid cell walls, these osteoblast-like cells have fluid cell membranes that can conform to a modulated substrate. We have further explored the concept of differential bacteria/tissue-cell adhesion using microgel particles synthesized by emulsion polymerization. These can be deposited onto biomaterials surfaces, including ones with significant 3-D topography, using electrostatic self assembly. In addition to the intrinsic differential adhesion between such a microgel-modified surface, bacteria, and tissue cells, the microgels can be electrostatically loaded with antimicrobials such as cationic peptides and antibiotics in order to actively kill bacteria while still preserving a surface conductive to tissue ingrowth.
MM5:
Session Chairs
Christian Hellmich
Dinesh Katti
Tuesday PM, November 29, 2011
Room 103 (Hynes)
2:30 PM - **MM5.1
Electrospun Scaffolds from Low Transition Temperature Polymers for Tissue Engineering and Drug Delivery.
Elizabeth Hedberg Dirk 1 2
1 Center for Biomedical Engineering, University of New Mexico, Albuquerque, New Mexico, United States, 2 Department of Chemical and Nuclear Engineering, University of New Mexico, Albuquerque, New Mexico, United States
Show AbstractElectrospinning is an inexpensive, simple technique that is used to create non-woven meshes for a variety of applications. It is a method that applies a very large electric field between a syringe pump filled with a solvated polymer with a high glass transition temperature and a grounded collection plate in order to produce micro- or nano-fibers. As the solvent evaporates the fibers are formed through entanglement of the polymer chains during flight. Recently we have developed a technique that enables polymers with low glass transition temperatures (below room temperature) to be electrospun. The recently developed technique uses a UV source to crosslink the polymer in situ in order to form micro- and nano-fiberous scaffolds. We have demonstrated in situ crosslinking with fumarate based biomaterials including poly(propylene fumarate) (PPF), poly (butylene fumarate) (PBF), and copolymers poly(propylene fumarate)-co-(propylene maleate) (PPFcPM) and poly(butylene fumarate)-co-(butylene maleate) (PBFcBM). We have further demonstrated that the rate of crosslinked polymer degradation is dependent on the polymer chemistry, for example 1,3-polybutylene fumarate degrades faster than 1,2-polypropylene fumarate. Control of the fiber size and pore density within the electrospun scaffold combined with control over polymer degradation chemistry provides a versatile materials platform that allows fine control over the material degradation rate, making it ideal for use in tissue engineering and drug delivery applications. Processing parameters of the in situ crosslinking during electrospinning as well as the degradation rates of the fumarate polymers will be discussed.
3:00 PM - **MM5.2
Bone Fibrillogenesis and Mineralization: Quantitative Analysis and Implications for Tissue Elasticity and Tissue Engineering.
Christian Hellmich 1 , Jenny Vuong 1
1 Deparment of Civil Engineering, Vienna University of Technology, Vienna Austria
Show AbstractBone tissue engineering has become a huge field, a great variety of different material systems have beenexplored for their potential use as bone tissue engineering scaffolds. Quite naturallyamong all these materials, such based on the actual elementary components of bone,i.e. on hydroxyapatite, collagen and water, may play an important role among all theaformentioned material classes, since one might well expect that such materials mighttend to be able to reproduce both the astonishing mechanical properties of bone andthe material’s biological features. But even if the materials’ basic components are chosen, the questionsregarding their mixing characteristics, i.e. of the concentration of the individualcomponents, remain to be answered. A close inspection of century-long chemical investigationsclearly shows that there is a larger variety of compositions, ranging all theway from (almost) unmineralized osteoid in early deposition stages to tissues consistingmainly of hydroxyapatite. careful analysis of the data, as to extract thechemical concentrations of hydroxyapatite, of water, and of organic material (mainlycollagen) in the extracellular bone matrix, reveals an astonishing fact: it appears thatthere exists a unique bilinear relationship between organic concentration and mineralconcentration, across different species, organs, and age groups, from early childhoodto senility: During organ growth, the mineral concentration increases linearly withthe organic concentration (which increases during fibrillogenesis), while from adulthoodon, further increase of the mineral concentration is accompanied by a decreasein organic concentration. These relationships imply unique mass density-concentrationlaws for fibrillogenesis and mineralization, which - in combination with micromechanicalmodels - deliver ’universal’ mass density-elasticity relationships in extracellularbone matrix – valid across different species, organs, and ages. They turn out as quantitativereflections of the well-instrumented interplay of osteoblasts, osteoclasts, osteocytes,and their precursors, controlling, in a fine-tuned fashion, the chemical genesisand continuous transformation of the extracellular bone matrix. Considerations ofthe aformentioned rules may strongly affect the potential success of tissue engineeringstrategies, in particular when translating, via micromechanics, the aformentionedgrowth and mineralization characteristics into tissue-specific elastic properties.
3:30 PM - MM5.3
Controlled Assembly of Carbon Nanotubes with Collagen Using a Novel Electrochemical Process.
Xingguo Cheng 1 , Vasiliki Poenitzsch 1 , Rena Bizios 2
1 Microencapsulation and Nanomaterials, Southwest Research Institute, San Antonio, Texas, United States, 2 Biomedical Engineering, University of Texas at San Antonio, San Antonio, Texas, United States
Show AbstractCarbon nanotube-based materials have potential for bone/cardiovascular,tednon/ligament,neural tissue engineering and regeneration applications. The introduction of CNTs into traditional biomaterial scaffolds offers the possibility of improved mechanical strength, durability, directed cell guidance, and controlled differentiation and migration of cells. Despite the exploding research regarding CNTs for biomaterial applications, there is lack of approach to control the orientation, packing density, and hierarchical organization of CNTs with biomolecules. One of the major challenges for effectively exploiting the remarkable mechanical and electric properties of CNTs in biomaterials is the controlled assembly of individual CNTs into useful macroscopic structures. Here we present the controlled assembly of CNTs with collagen biomolecules from nanoscale to macroscale by using a novel electrochemical process. In this process, both CNTs and collagen are charged due to pH gradient existing between two electrodes. Both CNTs and collagen are isoelectrically focused and packed into a dense structure. First, a fully dispersed CNTs and (topo)collagen mixture was formed by dispersing functionalized CNTs into dialyzed collagen solution. By using linear or plate electrodes, CNTs and collagen mixture was controlled assembled into 1D aligned fibers or 2D planarly-aligned sheet. Finally, these macroscopic CNTs/collagen structures were characterized by SEM, Raman Spectroscopy, Nano-indentation, and cell-based biocompatiblity assays. Our results indicated that the electrochemical process can control the assembly of both CNTs and collagen simultaneously. In the aligned fiber, both collagen and CNTs are aligned along the fiber direction. In the aligned sheet, both collagen and CNTs are randomly distributed onto the plane. Moreover, CNTs-collagen fiber or sheet with high CNTs loading and packing density can be achieved using this process. Nano-indentation indicated that the mechanical properties of CNTs-collagen scaffold is dramatically improved due to this unique co-assembly process. Finally, cell biocompatiblity test indicated that CNT-collagen has very good cell biocompatiblity.This study indicated that controlled assembled CNTs-collagen material fabricated by the electrochemical process might be useful as novel tissue scaffolds with tunable composition, anisotropy, and biomechanial properties. Our future efforts will be directed toward the application of aligned CNTs/collagen fiber as tendon/ligament/nerve graft, and aligned CNTs/collagen sheet for connective tissue repair and regeneration scaffold.
4:00 PM - **MM5.4
Direct Laser Write for Tissue Engineering Scaffold Manufacture.
Andrew Gill 1 , Kiran Pawar 1 , John Haycock 1 , Frederik Claeyssens 1
1 Materials Science and Engineering , University of Sheffield, Sheffield United Kingdom
Show AbstractA critical component for successful engineering of complex three-dimensional (3D) tissue from a cell source is the production and utilisation of the appropriate 3D scaffold. Indeed, cells on a flat surface grow typically in a monolayer fashion, while 3D cell culture can only be achieved via cell growth in a 3D environment or scaffold. The success of such scaffolds in tissue engineering applications depends critically on their mechanical and surface properties and microstructure, parameters dictated by the specific cell/tissue type grown on them. The specific microstructure of the scaffold is not only cell type dependent, but also needs to account for optimal perfusion via allowing for/enabling vascularisation.To optimally control these parameters we use laser based direct write techniques, in which a scaffold can be produced from a computer file via computer aided design/manufacturing (CAD/CAM). We combine these direct write techniques with in house synthesized polylactide (PLA) and polycaprolactone (PCL)-based liquid prepolymers.[1-2] These prepolymers are rendered photocurable via attaching methacrylate groups to the hydroxyl end groups. These resins cure under UV-irradiation (single-photon) and under femtosecond IR irradiation (two-photon). In 2-photon polymerisation the material polymerises only at the focal point of the optical set-up enabling real 3D Direct Laser Write (DLW) via scanning the laser through the material. Our results show that the photocurable resin can be readily structured with both (i) a femtosecond Ti:sapphire laser and (ii) the frequency doubled output of a cheaper sub-nanosecond (~0.5 ns) Nd:YAG laser. Both these laser set-ups produced structures with sub-micrometer resolution. Additionally, macroscopic (5 mm-sized) structures could be produced with ~10 micrometer resolution within a feasible timescale. We will discuss the use of these polymers to produce user defined 3D structures via both conventional stereolithography and 2-photon polymerization. We will further highlight the use of these photocurable biodegradable resins for manufacturing neural guidance conduits. [1] F. Claeyssens, et al. "Biodegradable Structures Fabricated by Two-Photon Polymerization," Langmuir 25, 3219-3223 (2009)[2] A.A. Gill and F. Claeyssens:“3D structuring of biocompatible and biodegradable polymers via stereolithography.” Methods in molecular biology (Clifton, NJ), 695:309-321 (2010)
4:30 PM - **MM5.5
Conductive Electrospun Porous Scaffolds as Potential Neural Interface Materials.
Shawn Dirk 1 , Kirsten Cicotte 2 1 , Elizabeth Hedberg-Dirk 2 3 , Stephen Buerger 4 , Patrick Lin 5 , Gregory Reece 6
1 Organic Materials Department, Sandia National Laboratories, Albuquerque, New Mexico, United States, 2 Center for Biomedical Engineering, University of New Mexico, Albuquerque, New Mexico, United States, 3 Chemical and Nuclear Engineering Department, University of New Mexico, Albuquerque, New Mexico, United States, 4 Intelligent System Controls Department, Sandia National Laboratories, Albuquerque, New Mexico, United States, 5 Department of Orthopedic Oncology, The University of Texas MD Anderson Cancer Center, Houston , Texas, United States, 6 Department of Plastic Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States
Show AbstractOur overall intent is to develop improved prosthetic devices with the use of nerve interfaces through which transected nerves may grow, such that small groups of nerve fibers come into close contact with electrode sites, each of which is connected to electronics external to the interface. These interfaces must be physically structured to allow nerve fibers to grow through them, either by being porous or by including specific channels for the axons. They must be mechanically compatible with nerves such that they promote growth and do not harm the nervous system, and biocompatible to promote nerve fiber growth and to allow close integration with biological tissue. They must exhibit selective and structured conductivity to allow the connection of electrode sites with external circuitry, and electrical properties must be tuned to enable the transmission of neural signals. Finally, the interfaces must be capable of being physically connected to external circuitry, e.g. through attached wires.We have utilized electrospinning as a tool to create conductive, porous networks of non-woven biocompatible fibers in order to meet the materials requirements for the neural interface. The biocompatible fibers were based on the known biocompatible material poly(dimethyl siloxane) (PDMS) as well as a newer biomaterial developed in our laboratories, poly(butylene fumarate) (PBF). Both of the polymers cannot be electrospun using conventional electrospinning techniques due to their low glass transition temperatures, so in situ crosslinking methodologies were developed to facilitate micro- and nano-fiber formation during electrospinning. The conductivity of the electrospun fiber mats was controlled by controlling the loading with multi-walled carbon nanotubes (MWNTs). Fabrication, electrical and materials characterization will be discussed along with initial in vivo experimental results. Sandia is a multiprogram laboratory operated by Sandia Corporation, a Lockheed Martin company, for the United States Department of Energy under contract DE-AC04-94AL8500.
5:00 PM - **MM5.6
Anisotropic, Patchy Microspheres with Soft Protein Islets.
Steven Little 1 2 3 , Kaladhar Kamalasanan 1 , Siddharth Jhunjhunwala 1
1 Chemical Engineering and Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States, 2 Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States, 3 The McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
Show AbstractSurface anisotropy (i.e. uniform patterns of discrete functional moieties), is a common feature of many natural systems and a hallmark of functional efficiency. Specifically, a given discrete unit, with anisotropy of chemical or physical properties (e.g. adhesion, repulsion, enzymatic reactivity, energy conservation or transfer) will endow function through regular short-range variability, leading to the possibility for longer-range “orderliness”. Examples include (but are not limited to) atoms in the “functional” groups of a molecule, proteins such as enzymes, and even the biological signatures of “patchiness” on cell surfaces during tissue organization and immune responses. For these reasons, discrete, synthetic building blocks that mimic anisotropy seen in nature could increase efficiency in the areas of sensors, opto-electronic devices, modulators, and drug delivery systems. Here, we report a new and robust technique to produce ordered patches around microspheres via combination of solid and liquid-phase deposition. The solid component of this new technique employs the microspheres themselves in proximity to its neighbors to determine the resulting pattern. The organization of the particles with respect to one another may be as simple as particle doublets (one contact point between particles) to lines of particles (2 contact points per particle 180 degrees on opposite poles), to more complex formations that lead to any number of contact points between solid microspheres. The liquid phase component of the processing technique takes advantage of surface tension and dewetting such that solutions of masking material may be localized only to the contact points between microspheres. Any number of patch materials can be used including various polymers and even precipitated sugars, salts and even lipids. We have also recently demonstrated the ability to spontaneously form various microstructures with these anisotropic particles using a ratio of particles with various numbers of patches of biotin using a streptavidin trigger.
5:30 PM - **MM5.7
3D Printing of Fumarate Based Polymers.
Kirsten Cicotte 1 2 , Elizabeth Hedberg-Dirk 1 3 , Shawn Dirk 2
1 Center for Biomedical Engineering , University of New Mexico , Albuquerque , New Mexico, United States, 2 Organic Materials , Sandia National Labs, Albuquerque , New Mexico, United States, 3 Chemical and Nuclear Engineering , University of New Mexico , Albuquerque , New Mexico, United States
Show AbstractRecently, an inexpensive 3D lithography technique was developed by Professor Nicholas Fang at the University of Illinois where a projector is used in combination with a Powerpoint presentation to expose the liquid negative-tone photoresist 1,6-hexanediol diacrylate in a layer-by-layer fashion. We have used this inexpensive 3D printing technique to create 3D structures of fumarate based polymers including poly(propylene fumarate) PPF, poly (butylene fumarate) (PBF), poly(propylene fumarate)-co-(propylene maleate) (PPFcPM), and poly(butylene fumarate)-co-(butylene maleate) (PBFcBM). All the fumarate based polymers are viscous liquids which makes them ideal for the projector based lithography technique when used in combination with the photoinitiator bisphenyl(2,4,6-trimethylbenzoyl)-phosphine oxide (BAPO). Furthermore, the fumarate based materials are biocompatible and are suitable candidates for tissue engineering applications. Polymer synthesis, lithography processing parameters as well as cell studies will be presented and compared to other techniques such as electrospinning, which have been recently used to fabricate tissue engineering scaffold structures from fumarate-based polymers. Sandia is a multiprogram laboratory operated by Sandia Corporation, a Lockheed Martin company, for the United States Department of Energy under contract DE-AC04-94AL8500.
Symposium Organizers
Roger Narayan University of North Carolina and
North Carolina State University
Seeram Ramakrishna National University of Singapore
Vipul Dave Cordis Corporation, a Johnson & Johnson Company
Donglu Shi University of Cincinnati
Sungho Jin University of California-San Diego
Wednesday AM, November 30, 2011
Room 103 (Hynes)
9:00 AM - **MM6.1
Nanostructured Bio-Functional Calcium Phosphate Based Systems.
Prashant Kumta 1 2 3
1 Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States, 2 Chemical and Petroleum Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States, 3 Oral Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
Show AbstractNanotechnology is a revolutionary area that has impacted several areas of materials science and engineering. The reduced system dimensionalities and nano-crystalline grain sizes have led to some uniquely distinct phenomena that were hitherto unknown, serving as a harbinger to a new class of functional devices. The potential ramifications of nanotechnology transcend the traditional domains of materials science impacting all aspects of materials’ properties — from electronics, optics, electro-optics, magnetism, spin-tronics, electrochemistry to even bio-functionality and tissue engineering. Nanostructures and nanocomposites have thus been synonymous in various areas of electronics, optics, magnetic and even biotechnology. The ability to generate nano-sized carriers for growth factors, proteins and plasmid DNA for non-viral gene delivery has been garnering significant interest. Accordingly, we have developed innovative approaches to synthesize bio-ceramic nano-particles, bioceramic-biological material composites, and novel forms of biocompatible calcium phosphate (CaP) putties under physiological conditions. These nanoscale complex systems show excellent affinity for binding and condensing plasmid DNA (pDNA) leading to excellent in vitro gene transfection indicative of their potential in non-viral gene delivery. The nano-particle complexes when incorporated into the cement forming mix results in a novel nanostructured, bioactive functional cement under physiological conditions at neutral pH highly amenable for incorporating signaling molecules, biologics and cells. The complex engineered system when implanted in animal models shows great promise for mineralized tissue regeneration. The presentation will finally conclude with the implications of these novel materials in the area of biotechnology for mineralized and even stem cell tissue engineering.
9:30 AM - **MM6.2
Potential Bone Replacement Materials Prepared by Two Methods.
Joanna McKittrick 1 2 , Steve Lee 2 , Grace Lau 3 , Po-Yu Chen 4 , Ekaterina Novitskaya 2 , Tony Tomsia 3
1 Mechanical and Aerospace Engineering, University of California, San Diego, La Jolla, California, United States, 2 Materials Science and Engineering Program, University of California, San Diego, La Jolla, California, United States, 3 , Lawrence Berkeley Laboratory, Berkeley, California, United States, 4 4Department of Materials Science and Engineering, National Tsing Hua University, Hsinchu Taiwan
Show AbstractThis talk focuses on the fabrication and analysis of bioinspired bone composites using either a biogenic or synthetic hydroxyapatite scaffolds. Bovine femur samples were deproteinized in a sodium hypocholride solution, which resulted in a stand-alone structure consisting of a porous network of hydroxyapatite crystals. The synthetic scaffolds were prepared by freeze-casting of commercially available hydroxyapatite, with similar porosities to the natural scaffolds. The scaffolds were filled with various polymer resins and tested in compression. Comparisons between the composites, orientation effects and microscopic evaluation will be presented.
10:00 AM - **MM6.3
Nature-Inspired Hybrid Structural Materials.
Antoni Tomsia 1 , Eduardo Saiz 2
1 Materials Sciences Division, Berkeley Lab, Berkeley, California, United States, 2 Department of Materials, Imperial College London, London United Kingdom
Show AbstractThe need for a synthetic implant to address multiple physical and biological factors imposes tremendous constraints on the choice of suitable materials. There is a strong belief that nanoscale materials will produce a new generation of implant materials with high-efficiency, low cost, and high volume. Metallic implants have been successfully used for decades but they have serious shortcomings related to their osseointegration and the fact that their mechanical properties do not match those of bone. The promising avenue to improve the osseointegration is through surface engineering that would include nanoscale topography and/or coatings for better and faster osseointegration of implants designed to function for the lifetime of the individual. Current surface chemistries and morphologies are controlled, at best, at the micron level, but tissue response is mainly dictated by processes controlled at the nanoscale. Understanding and controlling interfacial reactions at the nano level is the key to developing new implant surfaces that will eliminate rejection and promote adhesion and integration to the surrounding tissue. In this presentation we describe attempts to develop a range of bone- and nacre-like structural materials using a new freeze-casting technique, which utilizes the intricate structure of ice to create hybrid materials with complex lamellar and/or mortar and brick structures modeled across several length-scales, including nanoscale. Our results show ceramic-polymer and ceramic-metal hybrid materials with toughness well in excess of those expected from a rule of mixtures construction can be fabricated. The surface architecture and properties of the synthetic materials are compared to their natural counterparts in order to identify the mechanisms that control mechanical behavior over multiple dimensions and propose new design concepts to guide the synthesis of hybrid/hierarchical structural materials with unique mechanical responses. The ultimate goal is to produce materials and therapies that will bring state-of-the-art technology to the bedside and improve the quality of life and current standards of care. This work was supported by the National Institute of Health (NIH/NIDCR) grant number 1 R01 DE015633.
10:30 AM - MM6.4
Effect of Glutaraldehyde on Properties of Collagen Fibril Membranes Prepared from Fish Scale Collagen.
Zhefeng Xu 1 , Toshiyuki Ikoma 1 , Tomohiko Yoshioka 1 , Motohiro Tagaya 1 , Rena Matsumoto 2 , Toshimasa Uemura 2 , Junzo Tanaka 1
1 Department of Metallurgy and Ceramics Science, Tokyo Institute of Technology, Tokyo Japan, 2 Nanosystem Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba Japan
Show AbstractCollagens extracted from mammal animals such as bovine and porcine gradually limit the usage of collagen productions in the fields of biological, biomedical, food and cosmetic, since mammal animals have common virus with human being. Therefore, collagen from animate beings without amphixenosis virus has been requested. Fish is a favorable source due to its large scale aqua-farming and no amphixenosis virus. In particular, tilapia fish scale satisfies essential conditions of collagen in industrial usage such as large scale production, high denaturation temperature (309 K), and low impurity of fat.In this study, collagen fibril membranes (CFMs) as scaffold were prepared from tilapia fish scale collagen by using a facile drying method, and were cross-linked with a glutaraldehyde (GA) gaseous in order to enhance the mechanical property. The micro- and nano-structures, degree of crosslinking, denaturation temperature, and tensile strength for CFMs were evaluated and discussed.The density and thickness of the CFMs prepared were 0.51 ± 0.04×10-4 mg/cm3 and 50 ± 5 µm, respectively. Atomic force microscopic images exhibited the characteristic striped pattern at 67 nm of native collagen fibrils. The fibrogenesis of collagen improved denaturation temperature at 10 K compared with that of collagen molecular dispersed in an acidic solution. The denaturation temperatures of the CFMs treated with different duration times of GA gaseous were varied in three steps at the degree of crosslinking. In the first step i.e. the degree of crosslinking is less than 20.4 %, the denaturation temperatures of the CFMs were slightly increased compared with that of non-crosslinked CFM. In the second step i.e. the degree of crosslinking is greater than 20.4 % and is less than 43.0 %, the denaturation temperatures of the CFMs were linearly increased with the degree of crosslinking. The maximal denaturation temperature of the CFMs with the degree of crosslinking of 43.0 % in the third step was 348.3 K. The tensile strength of the CFMs was also classified into three groups including non-crosslinked CFM. The CFMs at the degree of crosslinking less than 33.3 % was slightly increased compare with that of the non-crosslinked CFM. In contrast, the degree of crosslinking exceeded 43.0 %, the tensile strength of CFMs were remarkably increased at 68.1 MPa. The microstructure of CFMs with degree of crosslinking of 43.0 % shows that the connection between collagen fibrils with GA molecular was remarkably increased compared with that of non-crosslinked CFMs from the scanning electron microscopy.The CFMs with the high density were successfully prepared. The tensile strength of CFMs was classified into three groups including non-crosslinked CFMs, which was apparently correlated to the degree of crosslinking.
11:00 AM - **MM6.5
What Roles do Nanostructures Play in the Strengthening and Toughening of Nacre? Lessons from Nature.
Xiaodong Li 1
1 Department of Mechanical Engineering, University of South Carolina, Columbia, South Carolina, United States
Show AbstractNacre is a natural nanocomposite with superior mechanical strength and eminent toughness. What is the recipe that Mother Nature uses to fabricate nacre? What roles do the nanoscale structures play in the inelasticity and toughening of nacre? Can we learn from this to produce nacre-like nanocomposites? The recent discovery of nanoparticles in nacre is summarized, and the roles these nanoparticles play in nacre’s strength and toughness are elucidated. It was found that rotation and deformation of aragonite nanoparticles are the two prominent mechanisms contributing to energy dissipation in nacre. The biopolymer spacing between nanoparticles facilitates the particle rotation process. Individual aragonite nanoparticles are deformable. Dislocation formation together with deformation twinning were found to play an important role in the plastic deformation of individual nanoparticles, contributing remarkably to the strength and toughness of nacre upon dynamic loading. This talk also presents future challenges in the study of nacre’s nanoscale structure and mechanical properties.
11:30 AM - **MM6.6
Processing of Recombinant Spider Silk Proteins.
Thomas Scheibel 1
1 Biomaterials, Universität Bayreuth, Bayreuth Germany
Show AbstractProteins reflect one fascinating class of natural hierarchically structured substances. The interplay between the polymeric building blocks is intriguing, and for long researchers tried to unravel the underlying concepts. One well-known example is spider silk with excellent mechanical properties such as strength and toughness. Most spider silks are used for building the web, which reflects an optimized trap for flying prey. In order to analyze the potential of the underlying spider silk proteins, we have developed a recombinant system using bacteria as hosts which produce silk proteins mimicking the natural spider silks. Recombinant proteins enable detailed analysis of the fiber formation process. Additionally, silk proteins can be processed into other morphologies such as hydrogels, spheres or films with tailored properties for biomedical applications.
12:00 PM - **MM6.7
Multifunctional Thin Coatings Formed on NiTi Shape Memory Alloy through Plasma Immersion Ion Implantation and Deposition (PIIID).
Min Wang 1
1 Department of Mechanical Engineering, The University of Hong Kong, Hong Kong Hong Kong
Show AbstractDue to their unique shape memory and superelastic properties, NiTi shape memory alloys (SMAs) are promising metallic biomaterials for making cardiovascular, orthopaedic and dental devices. However, their long-term biocompatibility and wear properties give rise to concerns about their long-term clinical applications. In long-term implantation, Ni ions released from NiTi SMA implants and corrosion products on the implants can trigger toxic, allergic and potentially carcinogenic effects. Furthermore, long-term wear and wear debris from orthopedic joint implants can initiate a cascade of complex cellular events that will result in aseptic loosening of the prosthesis. For some applications in orthopaedics and dentistry, NiTi SMA implants also need to possess desirable bioactivity (osteoconductivity). Fabricating a dense and uniform coating on the surface of NiTi SMA implants using an appropriate surface modification technique is an effective way to achieve a good combination of bioactivity, long-term biocompability, corrosion resistance and mechanical properties (including wear resistance) for the implants. In recent years, many surface modification techniques, including H2O2-oxidation, biomimetic deposition, electrochemical deposition and magnetron sputtering, have been investigated for the fabrication of novel and high quality coatings for NiTi SMAs. Plasma immersion ion implantation and deposition (PIIID) is a hybrid process that involves both ion implantation and deposition and usually forms an atomically intermixed layer between the metal substrate and coating, resulting in high bonding strength of coatings. Coatings produced via PIIID are relatively thick as compared to coatings made by other ion beam techniques. Another advantage of PIIID is that it is a relatively low temperature process (below 200°C) and therefore, it can effectively avoid the dimensional changes of metal implants resulting from high temperature processes and also minimize the degradation of the shape memory property, which can be caused by the plasma immersion ion implantation (PIII) technique. In this investigation, PIIID was employed to form a series of composite coatings, such as (Ti, O, N)/Ti and (Ti, Si, O, N)/Ti coatings, on a NiTi SMA (50.8 at.% of Ni). The coatings were relatively thick (around 1 micron, as compared to the coating thickness of tens of nanometers achieved by PIII), uniform and dense. They strongly adhered to the NiTi SMA substrate. Both corrosion resistance and wear resistance of NiTi SMA were greatly improved by the coatings. In vitro assessment indicated that the biological performance of coated NiTi SMA was also significantly enhanced.
12:30 PM - **MM6.8
Laser Direct-Writing of Biomaterials for Engineered Micro-Scale Constructs.
Tram Phamduy 1 , Andrew Dias 1 , Nurazhani Abdul Raof 3 , Nathan Schiele 1 , Janet Paluh 3 , David Corr 1 , Yubing Xie 3 , Douglas Chrisey 2 1
1 Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, New York, United States, 3 College of Nanoscale Science and Engineering, University at Albany-SUNY, Albany, New York, United States, 2 Materials Science, Rensselaer Polytechnic Institute, Troy, New York, United States
Show AbstractThe stem cell niche is an in vivo micro-environment that subjects cells to a multitude of disparate biological stimuli (e.g., cell-cell interactions, soluble factors, biomechanical cues). Understanding and controlling the stem cell niche is the holy grail for engineering cellular constructs by creating artificial micro-environments which drive stem cells towards desired maintenance or differentiation. A critical aspect of designing a construct from artificial niches is the ability to spatially control the placement of biomaterial units (e.g., protein solutions, cells, extracellular matrix). Laser direct-writing (LDW) enables the deposition of ‘voxels’ (volume pixels) into spatially-precise, in vitro patterns. The ability to deposit stem cells and individual cell-encapsulated hydrogel micro-beads provides a unique platform for synthesizing a combinatory library of stem cell micro-environments to better understand the factors that drive stem cell differentiation. Our lab has demonstrated the ability to deposit mouse embyronic stem cells (mESCs) and mESCs encapsulated in alginate micro-beads with diameters ranging from 200-600 um. In addition, calcein/AM-EthD-1 (live/dead) and Oct-4 staining indicates that the mESCs are able to survive the transfer process and maintain ‘stemness.’ Altogether, we demonstrate the feasibility of LDW to print simple and complex patterns of mESCs and mESC-micro-beads to create engineered cellular constructs.
MM7:
Session Chairs
Cedric Ayela
Thomas Scheibel
Wednesday PM, November 30, 2011
Room 103 (Hynes)
2:30 PM - **MM7.1
Porous Microcantilevers for Enhanced Chemical Detection in Liquid Media.
Cedric Ayela 1 , Georges Dubourg 1 , Hélène Lalo 2 , Liviu Nicu 3 , Claude Pellet 1 , Isabelle Dufour 1 , Alexander Kuhn 2 , Karsten Haupt 4
1 MMM, IMS lab - CNRS, Talence France, 2 NSysA, ISM lab, Pessac France, 3 NBS, LAAS - CNRS, Toulouse France, 4 , UTC - UMR6022 - CNRS, Compiègne France
Show AbstractMicrocantilevers are widely used as chemical sensors for a variety of applications. Classically, they are functionalized by a sensitive coating ensuring selectivity towards analytes, while standard operating mode of such devices is based on their resonance, defining the sensitivity of the sensors. However, their use for the detection of ultra-low concentrations of analytes remains challenging, especially in liquid media where viscous damping occurs. Among other solutions, the limit of detection of cantilevers can be improved by increasing the number of receptors available for analyte binding.In this context, porous materials are being evaluated as a powerful alternative. Indeed, by creating 3D microstructures made of porous materials (organic or inorganic), the surface to volume ratio can be improved by several orders of magnitude, when compared to flat patterns. In the present work, we describe the improvement of the limit of detection of MEMS-based sensing platforms by creating inorganic and organic porous microcantilevers. First, concerning environmental analysis, biomimetic polymers based on molecular imprinting ("plastic antibodies"- MIPs) are used to create free-standing organic cantilevers. The porosity of this coating is provided by incorporating a co-porogenic agent (polyvinylacetate) into the prepolymerization mixture, so that imprinted cavities available for analyte binding are accessible in the volume of the 3D microstructure. Moreover, the cantilevers are made of MIPs in an all-organic approach, combining binding sensitivity and selectivity with a functional mechanical structure, avoiding energy losses due to the interface between structural and sensitive layers.A new approach is proposed for the patterning of MIPs based on shadow-masking. A flexible microstencil made of SU-8 combined with spray-coating allows deposition and patterning of the prepolymerization mixture in one step. With this method, matrices of MIP patterns are created with a resolution down to 10 µm. A similar approach is used for the elaboration of porous gold cantilevers for diagnostic applications. Indeed, starting from a patterned flat gold path, we have tested a method for the elaboration of 3D inorganic porous microstructures. It consists in the electrodeposition of gold through multilayered matrices of self-assembled silica nanobeads obtained by the Langmuir-Blodgett technique. The primary flat layer is patterned thanks to the stenciling method where thermal evaporation of gold is used. Then, for the elaboration of free-standing cantilevers, the structures (made of MIP or gold) are transferred onto SU-8 chips by using a SU-8 wafer-bonding process that is well-suited for the wafer-level fabrication of cantilevers, independently from the material used as structural layer. As a result, the performances of these original organic and inorganic porous cantilevers will be presented and compared to traditional MEMS sensors to demonstrate their application potential.
3:00 PM - MM7.2
Ink-Jet Printing of Cells to Fabricate Scaffold Free Cell Sheets for Clinical Applications.
Eason Sivayoham 1 , Rachel Saunders 2 , Timothy Woolford 1 , Brian Derby 2
1 University Department of Otorhinolaryngology - Head & Neck Surgery, Manchester Royal Infirmary, Manchester, Greater Manchester, United Kingdom, 2 The School of Materials, The University of Manchester, Manchester United Kingdom
Show AbstractThe production of autologous implants using in vitro cultured, confluent; keratinocyte cell sheets harvested from thermoresponsive polymer surfaces has been previously described1. The deposition of fibroblasts using a piezoelectric ink-jet printer has been shown to have no significant effect on cell metabolic function and replication2. The experiments presented here, demonstrate the viability of the utilization of ink-jet printing to produce patterned, confluent cell sheets harvestable from a thermoresponsive polymer culture surface.DOK keratinocyte cells were printed using a drop on demand piezoelectric printer (Microfab, Plano, TX, USA) at three different pulse amplitudes to assess post-printing viability. Proliferation of cells printed at 40, 60 and 80 V were monitored using the metabolic alamar blue assay and DNA assay. DOK cells were directly printed onto a thermoresponsive surface (upcell, Nunc) and allowed to proliferate to confluence. The cell sheets were then lifted and measured. Patterned cell sheets were fabricated by staining a DOK cell suspension and printing a patterned array. Each single layer pattern was generated by overprinting 20 times to help maintain hydration. Once the stained cells attached to the thermoresponsive surface then a layer of unstained keratinocyte cells were added to generate a self-standing patterned sheet.All cells demonstrated post printing viability and proliferated to confluence. The mean surface area of the printed cell sheet was 7.4cm2. This was more than 80% of the total surface area seeded. The DNA analysis demonstrated proliferation of printed cells over the time points studied whilst the metabolic activity of the printed samples demonstrated a dip at the second time point, but then increased over the next two time points. This may suggest an impairment of metabolic function imparted on the cells by the printing process. Stained cells were successfully printed into an array to create a patterned cell sheet.1. Nishida, K., et al. "Functional bioengineered corneal epithelial sheet grafts from corneal stem cells expanded ex vivo on a temperature-responsive cell culture surface." Transplantation 77.3 (2004):379-385.2. Saunders, R., J. Gough and B. Derby. "Delivery of human fibroblast cells by piezoelectric drop-on-demand inkjet printing." Biomaterials 29.2 (2008):193-203.
3:15 PM - MM7.3
Real Time and Noninvasive Oxygen Sensors Based on Microfluidic Produced Polydimethylsiloxane Microbeads.
Kunqiang Jiang 1 , Peter Thomas 2 , Don DeVoe 3 , Srinivasa Raghavan 4 1
1 Department of Chemistry and Biochemistry, University of Maryland-College Park, College Park, Maryland, United States, 2 Department of Bioengineering, University of Maryland, College Park, Maryland, United States, 3 Department of Mechanical Engineering, University of Maryland, College Park, Maryland, United States, 4 Department of Chemical and Biomolecular Engineering, University of Maryland, College Park, Maryland, United States
Show AbstractOxygen tension imposes profound effects in a variety of important chemical and biological activities, thus it is of critical significance to develop effective, accurate, high performance sensors to precisely monitor the amount of oxygen in real time. Besides, the desired sensing method should also be compatible with miniaturized, automatic instruments in order to achieve high throughput measurements. Here we report a novel type of particulate sensors with the capability to meet all of the above requirements. These specific particulate sensors are based on monodisperse Polydimethylsiloxane (PDMS) microbeads, which are produced through specific droplet microfluidic techniques and have been incorporated with oxygen-sensitive dyes to have the sensing ability.First of all we have developed a novel microfluidic platform to produce PDMS microbeads. A thermal-plastic microfluidic device with flow focusing configuration has been used as the droplet generator, and a flow of PDMS precursor mixture has been continuously dispersed into monodisperse microdroplets within a continuous phase of aqueous solution. Discrete PDMS microdroplets are produced thus and are collected in a glass vial thereafter, where they are subsequently cured thermally into stable microbeads. Their sizes can also be systematically varied in the range from 10 to 200 microns by adjusting the relative flow rate ratio as well as engineering the microfluidic channel sizes.By taking advantage of excellent properties of PDMS, including being inert, stable and transparent, these PDMS microbeads possess high application potential in many fields. Here we have used them as particulate carriers to produce oxygen sensors. To accomplish this target, we have integrated an oxygen-sensitive phosphorescent dye, Pt(II) meso-tetrakis (pentafluorophenyl)porphine (PtTFPP), into the dispersed solution in advance. As a result, final PDMS microbead products also contain PtTFPP and thus become sensitive to oxygen concentration. The relationship between oxygen concentration and emission intensity of PtTFPP phosphorescence strictly follows the Stern-Volmer equation, ensuring precise measurements of oxygen in real time. There are three important factors contributing to the high performance of our particulate oxygen sensors. First, the high gas permeability of PDMS (800 Barrer) allows rapid exchange of oxygen molecules through the entire textual matrix and thus ensures their fast response and high sensitivity. Additionally, their narrow size distribution provides excellent reproducibility among groups of individual particles, which is a crucial consideration for many applications. Moreover, since these PDMS sensors are themselves microsized and can also be produced in massive amount, they have the capability to be integrated with automatic detection systems, offering the possibility to carry out rapid, high throughput measuring of multiple samples in short time.
3:45 PM - **MM7.4
Biofabrication Technologies for Biomedical Applications.
James Yoo 1
1 , Wake Forest Institute for Regenerative Medicine, Winston-Salem, North Carolina, United States
Show AbstractAdvances in micro- and nano-scale processing technologies have provided various therapeutic opportunities in the field of medicine. While techniques developed for tissue engineering and regenerative medicine applications have had initial successes in building a number of tissues clinically, challenges still exist in developing complex tissue systems. One of the challenges that hamper rapid clinical translation is due to the lack of efficient delivery methods for cells and biomaterials. Living tissues maintain inherent multi-cellular heterogeneous structures, and rebuilding of such complex tissue structures requires subtle arrangements of different cell types and extracellular matrices at their specific anatomical target sites. Biofabrication using an inkjet printing technology has been proposed as a tool to address this endeavor. In this session novel and versatile methods of building tissue structures using biofabrication technology will be discussed. Development strategies that facilitate a rapid clinical translation will also be discussed.
4:15 PM - MM7.5
Effect of Carbon-Coated TiO2 Nanotube Surface Chemistry on Osteogenic Cell Behavior.
Karla Brammer 1 , Chulmin Choi 1 , Christine Frandsen 1 , Sungho Jin 1
1 Materials Science & Engineering, Univ. of California, San Diego, La Jolla, California, United States
Show AbstractSurface engineering of medical implants has attracted much attention in recent years. Particular attention has been paid to the positive effects that the physical environment of nanotopography has on cell behavior, yet direct comparisons of nanotopographic surface chemistry have not been fully explored. We have compared TiO2 nanotubes with carbon-coated TiO2 nanotubes, probing osteogenic cell behavior, including osteoblast (bone cells) and mesenchymal stem cell (MSC) (osteo-progenitor cells) interactions with the different surface chemistries (TiO2 vs. carbon) [1]. While the material surface chemistry of the nanotubes did not affect the basic cell appearance or viability (cell adhesion, growth or morphology), it had a major influence on the cell functionality. In particular, we noted a higher level of alkaline phosphatase (ALP) activity of osteoblast cells on the original TiO2 chemistry. In contrast, when osteogenic differentiation of osteo-progenitor cells was assessed on the TiO2 and C coated nanotube surfaces, it was the carbon chemistry that resulted in increased bone mineral deposition and bone matrix protein expression. It was observed in this study that: (a) chemistry plays a role in cell functionality, such as ALP activity and osteogenic protein gene expression (PCR); (b) different cell types may have different chemical preferences for optimal function. The ability to optimize cell behavior using surface chemistry factors has a profound effect on both orthopedic and tissue engineering in general. This study aims to highlight the importance of the chemistry of the carrier material in osteogenic tissue engineering schemes. [1] KS Brammer, C Choi, CJ Frandsen, et al, “Comparative Cell Behavior on Carbon Coated TiO2 Nanotube Surfaces for Osteoblasts vs. Osteo-progenitor Cells”, Acta Biomater. 7(6), 2697-2703 (2011).
4:30 PM - MM7.6
Biofilm Reduction by Carvacrol and Cinnamaldehyde Incorporated into Poly(Lactide-co-glycolide) (PLGA) Thin Films.
Jessica Schiffman 1 , Katherine Zodrow 2 , Menachem Elimelech 2
1 Chemical Engineering, University of Massachusetts Amherst, Amherst, Massachusetts, United States, 2 Chemical and Environmental Engineering, Yale University, New Haven, Connecticut, United States
Show AbstractIntensive research into antibacterial agents continues to be a pressing necessity as both microbial resistance and infectious diseases remain. Microorganisms continue to contaminate the surfaces of medical devices, hospital and dental equipment, wound healing scaffolds and textiles. Hence, there exists a continued demand for the development of broad spectrum antibacterial agents and materials that can deliver those agents. The plant based essential oils, carvacrol (CARV) and cinnamaldehyde (CINN) have demonstrated toxicity to a variety of microorganisms. In this work, various concentrations of the essential oils, CARV and CINN have been incorporated into poly(lactide-co-glycolide) (PLGA) thin films. PLGA, CARV, and CINN, as well as composite thin films containing the essential oils have been well characterized. Results indicate that the growth and morphology of Pseudomonas aeruginosa and Staphylococcus aureus biofilms are influenced by the PLGA-essential oil thin films.
4:45 PM - MM7.7
Engineering In Vivo like 3D Microenvironment for Studying Cell-Cell Communication between Pancreatic β Cells.
Wei Li 1 , Samuel Lee 2 , Soomin Kim 2 , Richard Lee 2 , Paula Hammond 1
1 Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States, 2 Harvard Stem Cell Institute and Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, Massachusetts, United States
Show Abstractβ cells are aggregated in the form of islets. Within these islets, EphA-Ephrin-A-mediated cell-cell communication on the surface of β cells inhabits basal insulin secretion and enhances glucose-stimulated insulin secretion (GSIS). β cells lose their glucose sensitivity if they are cultured using traditional 2D cell culture technique, partially due to the fact that the cell isolation process removes β cells from their native microenvironment. Herein, we present a novel strategy to build in vivo like 3D microenvironment for studying cell-cell interactions between β cells. In particular, we apply microfluific synthesize of poly(ethylene glycol) microgels grafted with EphA receptor and Ephrin-A ligands, and then further modify the microgels with pancreatic-tissue-specific extracellular matrix coatings. In order to mimic cell-cell communication in a controlled manner, β cells are cultured in direct contact with microgels with designed characteristics, such as the size, stiffness of microgels, concentration of modified ligands, cell density, etc. Preliminary results show good compatibility of microgels with mouse insulinoma (MIN6) cells and enhanced cell viability.
5:00 PM - MM7.8
Biofunctionalization of Diamond like Carbon Layers.
Jana Sommerfeld 1 , Thomas Keller 2 , Klaus Jandt 2 , Carsten Ronning 1
1 Institute for Solid State Physics, Friedrich Schiller University Jena, Jena Germany, 2 Institute for Materials Science and Technology, Friedrich Schiller University Jena, Jena Germany
Show AbstractMotivated by the many possibilities to establish diamond like carbon (DLC) layers for biomedical applications, we investigated their interaction with biological material like proteins. The used DLC layers have been prepared via mass separated ion beam deposition (MSIBD) on Si substrates. For this purpose, carbon ions were accelerated with 30 kV and focused by an electromagnetic system containing a 90° sector magnet for mass separation, diverse einzel lenses and an electric quadrupole. Before reaching the substrate, the ions were decelerated down to a few hundred eV and are thus not deeply implanted but deposited on the substrate. The sp3 content and therefore the 'diamond likeness' can be adjusted by the deposition energy (1). Additionally, nanometer scale patterning is possible by ion beam irradiation. Proteins were adsorbed from phosphate buffer solution onto the ion beam deposited DLC coatings. The DLC film surface was characterized by contact angle measurements and the adsorbed protein assembly was examined as a function of the sp3 content by atomic force microscopy (AFM).(1) Electronic and atomic structure of undoped and doped ta-C films, C. Ronning et al., 1997, Diamond and Related Materials, Vol. 6, pp. 830 - 834
5:15 PM - MM7.9
Comparison of Bactericidal Activities Using Metal-Organic Framework and Nano-Particles.
Jingbo Liu 1 , Wenjuan Zhuang 2 , Sajid Bashir 1 , Hong-Cai Zhou 2
1 Chemistry, Texas A&M University-Kingsville, Kingsville, Texas, United States, 2 Chemistry, Texas A&M University, College Station,, Texas, United States
Show AbstractThe recent deadliest outbreak of the bacteria is a driving force for us to develop bacericidal agents with high potency and long-term stability. Our research discoveries indicated that a novel cobalt (Co) based metal organic framework (MOF) is highly effective at inactivating microorganism due to its tunable molecular architectures and functionalities. A Gram-negative bacteria, Escherichia coli (E. Coli, DH5alpha and XL1-Blue) was selected as the model microorganism to evaluate the anitbacterial actvities of the Co MOF. In this motif, the Co serves as a central element and a novel tetrahedral octa-topic carboxylate ligand, tetrakis [(3,5-dicarboxyphenyl)-oxamethyl] methane acid as a chelating agent, leading to a new type of compound, defined as Co-TDMs. The high potency using Co-TDMs as disinfectant was determeind to be 10-15 ppm, within a shorter incubation time period (< 60 mins). Our previous work indicated that silver nanoparticles and silver modified TiO2 nanocomposites displayed lowest minimal bactericidal concentration (MBC, 2.5 ppm), however, nanoparticles required longer incubation time (> 4 hr). The electron microscopic images indicated that the Co-TDMs displayed distinctive grain boundaries and well-developed reticulates. The Co active sites rapidly catalyzed the lipid peroxidation, causing rapture of bacteria membrane and then the death of E. coli. This accomplishment will provide new paradigms to engineer MOFs applied in the biological fields due to their unique porous structure, mulitfunctioning radicals, along with their tunable properties.
5:30 PM - MM7.10
Water Dispersed Curcumin Nanoparticles and Micelles for Multiphoton Bioimaging.
Abhishek Kumar 1 2 , Lian Li 4 , Joshna Chittigori 3 2 , Lynne Samuelson 4 , Danniel Sandman 3 2 , Jayant Kumar 1 2
1 Physics, University of Massachusetts Lowell, Lowell, Massachusetts, United States, 2 Center for Advanced Materials, University of Massachusetts Lowell, Lowell, Massachusetts, United States, 4 , U. S. Army Natick Soldier Research, Development & Engineering Center, Natick, Massachusetts, United States, 3 Chemistry, University of Massachusetts Lowell, Lowell, Massachusetts, United States
Show AbstractMultiphoton fluorescence imaging is considered as an important technique in biological imaging due to its high resolution, and reduced scattering and absorption in the near IR region for biological samples. Recently, Curcumin, a polyphenol derived from the plant Curcuma longa, has attracted considerable attention because of its anti-oxidant and anti-tumor activity. Here we report the potential application of Curcumin as a bio-marker using two-photon spectroscopy and confocal microscopy. Colloidal solution of surfactants that form micelles in aqueous solution has been used to solubilize Curcumin in aqueous medium which is otherwise sparingly soluble. Reprecipitation technique has also been used to form Curcumin nanoparticles dissolved in aqueous medium. One- and two-photon fluorescence properties and confocal microscopy of the Curcumin nanoparticles and in micelles will be reported.
5:45 PM - MM7.11
Highly Effective Visible-Light Activated Self-Disinfecting Surfaces.
Ding Weng 1 , Hangfei Qi 2 , Ming Yan 1 , Ting-Ting Wu 2 , Ren Sun 2 3 , Yunfeng Lu 1 3
1 Chemical and Biomolecular Engineering, Univerysity of California Los Angeles, Los Angeles, California, United States, 2 Molecular and Medical Pharmacology, Univerysity of California Los Angeles, Los Angeles, California, United States, 3 , California NanoSystems Institute, Los Angeles, California, United States
Show AbstractVirus infections pose continuous threats to both military and civilian populations, such like HIV/AIDS, severe acute respiratory syndrome (SARS) virus, the scary pandemic avian influenza virus and the recent outbreak of H1N1 virus (swine Flu). Unlike bacteria of which infections can be effectively controlled by antibiotics, virus infections are still difficult to deal with, especially the influenza viruses due to their continuously varying combination of hemagglutinin and neuroaminidase. By utilizing the careful selection of a novel class of semiconductor nanocrystals as visible-light-activated disinfectants, herein we introduce a highly effective nanoparticle-coated surfaces that can inactivate influenza virus and other types of microbe pathogens rapidly, spontaneously and continuously using even only visible lights. These nanoparticle coatings show strong absorbance in the visible range, which enabling them to harvest more solar energy at high efficiency and can even work at artificial illuminate conditions without UV range. Compared with the Cd-containing nanocrystals, these nanocrystals are less toxic and environmentally friendlier. While comparing to titanium oxide nanoparticle-coatings, which are broadly used as commercial photosensitizer, huge improvement in disinfecting ability has been proved on A/PR/8/34 H1N1 influenza A virus under visible light illuminating condition. The disinfection mechanism has been proved as inactivating the virus' envelope proteins and probably also damaging their genetic materials. Besides influenza virus, hepatitis C virus (HCV) and E. Coli. were demonstrated to be inactivated too, which suggested that the application of this self-disinfecting surfaces was not limited to influenza virus but also other kinds of virus and bacteria pathogens. We believed that our study has pioneered an innovative approach to design highly effective,rapid, spontaneous and continuous disinfecting surfaces for a variety of microbes throughjudicious selection of visible-light-active coatings.
Symposium Organizers
Roger Narayan University of North Carolina and
North Carolina State University
Seeram Ramakrishna National University of Singapore
Vipul Dave Cordis Corporation, a Johnson & Johnson Company
Donglu Shi University of Cincinnati
Sungho Jin University of California-San Diego
MM8
Session Chairs
Himanshu Jain
Ulrike Wegst
Thursday AM, December 01, 2011
Room 103 (Hynes)
9:00 AM - MM8.1
High Throughput Synthesis of Biocompatible Fluorescent Microbeads with Highly Loaded Quantum Dots and Uniform Size.
Seung-Kon Lee 1 , Jinyoung Baek 1 , Klavs Jensen 1
1 Chemical Engineering, MIT, Cambridge, Massachusetts, United States
Show AbstractThere has been intense and longstanding interest in the use of biocompatible fluorescent microparticles for a variety of applications such as bio-imaging, drug delivery, biological assay,clinical diagnostics, optical encoding, laser and display pigment. Batch synthesis has been the method of choice for preparing fluorescent polymer particles due to practical advantages in productivity and accessibility, despite disadvantages in controllability and efficiency. In batch synthesis, multiple separated steps of synthesis, purification, loading and washing are required to prepare the particles. During this process, the amount and size of loadable materials is limited. Furthermore, an excessive portion of loading materials is wasted, which is especially problematic when expensive QDs or biomaterials are used. In this research, we will present production of highly uniform emulsions using harmonic breakup of jet with high Weber number (We) in a coflowing system. In jet mode breakup, axisymmetric laminar jet of inner fluid is broken into a train of uniform tiny emulsions. Ideal harmonic fluctuation formed by a well-defined microchannel leads to series of disconnection with regular interval from the periodic modal points. Since the jet diameter is relatively small and widely variable for given nozzle diameter, the jet mode allows low pressure drop, high production rate and wide range of controllability, simultaneously. Additionally, biocompatible fluorescent microspheres with high QD loading were achieved throughout a controllable size range of 10 ~ 100 μm and 3% of uniform size distribution using jet breakup. By incorporating large QDs having thick protecting shells, their optical properties were well maintained even at high concentrations.
9:15 AM - MM8.2
Mineralization of Dense Collagen Scaffolds using a Polymer-Induced Liquid-Precursor (PILP) Process.
Laurie Gower 1 , Yuping Li 1 , Taili Thula 1
1 Department of Materials Science and Engineering, University of Florida, Gainesville, Florida, United States
Show AbstractBone is a hierarchically structured composite, which at the nanostructural level consists of an assembly of collagen fibrils that are embedded with uniaxially-aligned nanocrystals of hydroxyapatite. Our studies have revealed that this nanostructure can be reproduced in vitro using a polymer-induced liquid-precursor (PILP) mineralization process. The polymeric additive consists of acidic polypeptides (e.g. polyaspartic acidic) that are a simple mimic of the non-collagenous proteins associated with bone and dentin. The high charge density of the polyanionic additive sequesters ion such that liquid-liquid phase separation occurs in the mineralization solution, forming nanodroplets of a hydrated amorphous mineral precursor. Infiltration of the nanodroplets into the collagen fibrils leads to intrafibrillar mineral, which is the foundation of bone nanostructure. Through optimization of various reaction parameters, compositions matching that of bone (over 70wt% mineral) have been achieved in reconstituted collagen scaffolds. Biogenic collagen matrices can also be mineralized by this process, such as rat tail tendon and demineralized bone; however, there are currently limitations in the depth of penetration that can be attained. While this process leads to a nanostructure that emulates that of bone, isolated rigid mineralized fibrils in a porous scaffold simply crush under an applied load. Therefore, we have been examining methods to create more densely packed collagen scaffolds. Here we show that a densified collagen matrix which resembles the extracellular matrix of primary bone can be created with a plastic compression technique. A range of crosslink densities were then examined, and surprisingly, the higher crosslinking enhanced the mineralization process. Through nanomechanical testing, it was found that these composites can achieve nanomechanical properties (such as modulus and hardness) comparable to primary fetal bone (in the dry state). However, the properties are much lower in the hydrated state due to the inherent microporosity that still remains. Current efforts are directed at developing methods to create more densely-packed collagen scaffolds, which will then enable mechanical reinforcement of the surrounding collagen fibrils, as occurs in bone.
9:30 AM - **MM8.3
Tailoring Solid Interfaces Using Engineered Peptides from Biocompatibility and Self-Assembly to Biomineralization.
Mehmet Sarikaya 1 , Candan Tamerler 1
1 MSE and Chemcial Engineering, University of Washington, Seattle, Washington, United States
Show AbstractProteins enable biology to be viable through molecular interactions. Using biology as a guide at the molecular dimensions, we biocombinatorially select, bioinformatically enhance and genetically tailor solid binding peptides and utilize them as molecular building blocks in carrying out molecular and nanomaterials science and engineering. Genetically engineered peptides for inorganic materials (GEPI) are used as bionanosynthesizers in biomaterialization, heterofunctional linkers to create thermodynamically stable interfaces between dissimilar materials, and as molecular assemblers for the targeted and directed assembly of nanobiomaterials towards addressable ordered architectures with genetically designed functions. Here, we will give an update of the utility of a variety of GEPIs in nanoinorganic formation for hybrid probe design and bionanosensors; biofunctionalization of implants, biomineral formation for tissue regeneration and restoration, and in peptide-enabled nanobioelectronics and -nanobiophotonics to demonstrate the expanding paradigm in nanobiotechnology and nanomedicine. Primary funding is by NSF-MRSEC and BioMat Programs
10:00 AM - **MM8.4
Ice-Templated Hybrid Materials.
Ulrike G.K. Wegst 1
1 MSD, LBNL, Berkeley, California, United States
Show AbstractFreeze-casting, a process that uses the solidification of a liquid carrier such as water for templating, has in recent years been discovered as a route to create highly porous hybrid materials with complex, hierarchical architectures. Freeze-casting is highly attractive for the manufacture of materials for applications that range from scaffolds for tissue engineering to structures for energy generation because it offers several advantages over other techniques. One advantage is that all classes of materials (polymers, ceramics, metals and their composites) can be shaped with it; another is that materials can be processed with benign, biocompatible liquid carriers; a third is that the resulting hierarchical microstructures can be carefully controlled by both the physical and chemical properties of the components used and the processing parameters such as the cooling rate; finally advantage can be taken of component self-assembly during solidification. The amount, type, size and geometry of the particles and the type of liquid carrier determine the slurry’s viscosity and amount of sedimentation as well as the slurry’s thermal properties and freezing behavior. In combination with the freezing front velocity and additives, they also determine pore connectivity and morphometry. The thickness and spacing of the cell walls and the size and the number of the material bridges between them can be controlled, as can be the cell wall’s bulk and surface properties, and thus the materials interaction with a second phase. This is important for the manufacture of composites by infiltration or for the optimization of the interaction between scaffold and native tissue in biomedical applications. As a result, the freeze-casting process is ideally suited for the custom-designed manufacture of complex, hybrid materials with that emulate in synthetic materials multi-level hierarchical composite structures, which are thought to be the origin of the mechanical property amplification which is frequently observed in biological materials.
10:30 AM - MM8.5
Mechanical Behavior of Electrospun Chitosan Fibers.
Amalie Donius 1 , Marjorie Austero 1 , Caroline Schauer 1 , Ulrike G. Wegst 1
1 Materials Science & Engineering, Drexel University, Philadelphia, Pennsylvania, United States
Show AbstractPolymer fibrous mats have attracted research attention for applications in tissue engineering due to their ability to be tuned and provide appropriate structural, chemical, and mechanical cues. Through the use of a novel one-step method of crosslinking electrospun fibers, a randomly oriented network of fibers with enhanced properties can be created. This processing route is highly attractive since it gives rise to fibrous mats that mimic the architecture and length scale of the natural extracellular matrix. Chitosan, a derivative of chitin, the second most abundant polysaccharide, is the ideal biopolymer for such an application and processing technique because of its biocompatibility, resorbability, availability, and solubility. Different crosslinkers were used for the one-step process. Each was found to change both fiber diameter and mat morphologies in addition to the chemical stability of the tissue scaffolds and their mechanical properties such as stiffness, strength and work to fracture, which were determined in tension. In addition to initial crosslinking, post-spinning activation of the crosslinkers by heat, for example, was found to further affect the fiber and mat structure, and as a result also their mechanical performance. The structure-property-processing correlations determined through this research will aid to tailor the chemical stability, mat morphology and mechanical performance of electrospun fiber mats for a given application.
11:00 AM - **MM8.6
Dental Restoration Enabled by Additive Manufacturing: Slurry Micro-Extrusion.
Leon Shaw 1 , Jiwen Wang 2
1 , University of Connecticut, Storrs, Connecticut, United States, 2 , Enigmatics, Inc., College Park, Maryland, United States
Show AbstractA solid freeform fabrication procedure for human dental restorations via a slurry micro-extrusion process is described. A dental porcelain slurry is developed with pseudoplastic property and moderate viscosity, which permits the slurry to be extruded at low extrusion pressure and have good shape-keeping ability. A green tooth can be produced by this method directly from a CAD digital model in 30 min. The sintering shrinkage of the green tooth is uniform. Microstructure of the sintered tooth is identical to that made via the traditional dental restoration processes. This new dental restoration process presents potentials to provide dental patients with better, faster and less expensive service. The other potentials and future direction for slurry micro-extrusion will be discussed.
11:30 AM - **MM8.7
Processing of Nano-Macro Porous Bioactive Glass for Biomedical Applications.
Himanshu Jain 1 , Shaojie Wang 1 , Hassan Moawad 1 , Rui Almeida 2
1 Department of Materials Science and Engineering, Lehigh University, Bethlehem, Pennsylvania, United States, 2 Eng. Química e Biológica/ICEMS, Instituto Superior Técnico, Lisbon Portugal
Show AbstractIt is now well established that certain biomedical applications would benefit, even require, biocompatible solids containing a broad range of porosity, varying in size from a few nm to 100s of micrometers. For example, bioscaffolds for tissue regeneration should have interconnected pores larger than ~100μm to allow infiltration by cells, blood vessels, collagen fibers, etc. At the same time, nanoscale porosity is needed to match the degradation rate of the scaffold with the rate of tissue growth. Nanoporosity is also shown to enhance cell response under in vitro conditions. Thus, nano-macro porous bioactive glass appears to be an ideal candidate for use as scaffold for bone regeneration. Recently, certain glass compositions are shown to be also useful for soft tissue regeneration and wound healing. The creation of pores differing in size by several orders of magnitude is a challenging problem of material processing. We have pursued its novel solutions by exploiting multi-scale phase separation, followed by the selective removal of one or more phases by leaching or evaporation. Two independent approaches have been pursued utilizing the classic melt-quench and sol-gel methods of glass preparation, respectively. Glass compositions and processing conditions are identified, which lead to spinodal decomposition that is required for the interconnectivity of pores. Typically, bimodal or multi-modal porosity is obtained with pores ranging from ~10 nm to ~100 μm, and it is possible to control the nano and macro porosities independently for tailoring to the needs of a specific patient or application. However, if pores >100 μm are needed, additional fabrication processes have to be introduced. This presentation will review and compare the pros and cons of the currently available methods for fabricating nano-macro porous bioactive glass structures.
12:00 PM - MM8.8
Directional Cell Migration in One-Way Microchannels.
Young-Gwang Ko 1 , Carlos C. Co 1 , Chia-Chi Ho 1
1 Department of Chemical and Materials Engineering, University of Cincinnati, Cincinnati, Ohio, United States
Show AbstractEarlier, we have reported a gradient-free approach for controlling the simultaneous directional migration of unlimited number of cells over unlimited distances through Microarray Amplification of Natural Directional Persistence (MANDIP).1 Here, we will present a new three-dimensional analogue, Topographical Amplification of Natural Directional Persistence (TANDIP) that can direct the continuous migration of individual cells in channels fabricated on three-dimensional biomaterials. The directional cell migration for different topographic designs is demonstrated by time-lapse imaging of NIH 3T3 fibroblasts, and human microvascular endothelial cells (HMVEC). The role of RhoGTPases that mediate the spatial positioning of motile processes in response to physical interactions between cells and microchannels were probed by fibroblast mutants with constitutively activated Rac, Rho, or Cdc42. Cell migration speed increases with increasing interconnection angle of the channels in all tested cell types. This new method to guide directional cell migration and speed has significant potential implications in the design of scaffolds for tissue engineering and probing cell migration in three dimensions.(1)Kumar G, Co CC, Ho CC, “Steering Cell Migration Using Microarray Amplification of Natural Directional Persistence”, Langmuir (2011) p3803.
12:15 PM - **MM8.9
Multiscale Science of Protein Materials in Extreme Conditions and Disease.
Markus Buehler 1
1 Civil and Environmental Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States
Show AbstractBiology efficiently creates hierarchical structures, where initiated at nano scales, are exhibited in macro or physiological multifunctional materials to provide a variety of functional properties that include: structural support, force generation, catalytic properties, or energy conversion. This is exemplified in a broad range of biological materials such as hair, skin, bone, spider silk or cells. For instance, despite its simple building blocks spider silk is one of the strongest, most extensible and toughest biological materials known, exceeding the properties of many engineered materials including steel. This is particularly puzzling since despite its great strength, spider silk is made of some of the weakest chemical bonds known, H-bonds. Using a bottom-up computational approach that spans all the scales from nano (protein) to macro (spider web) we have discovered that the great strength and extensibility of spider silk can be explained based on its particular structural makeup, which involves several hierarchical levels. Thereby, the structural confinement of H-bonds into ultra-small beta-sheet nanocrystals with dimensions of only a few nanometers is a key aspect to overcome the intrinsic limitations of H-bonds, creating mechanically strong, tough and resilient cross-linking domains between a semi-amorphous phase composed of 31 protein helices. Our work unveils a material design strategy that enables silks to achieve superior material properties despite its simple and structurally inferior material constituents. Exploiting this concept could lead to a novel materials design paradigm, where enhanced functionality is not achieved using complex building blocks but rather through the utilization of universal repetitive constitutive elements arranged in hierarchical structures that range from the atomistic scale to macroscopic spider webs. We present approaches towards the design of adaptable, mutable and active materials that rely on simple, abundant and cheap building blocks to realize highly functional materials. Applications specifically to the design of materials from mechanically inferior materials such as silica and silica as found in diatoms or sea sponges are discussed, and opportunities for de novo materials design are outlined based on utilizing the universality-diversity-paradigm discovered in biological materials. We review the application of category and graph theory to make quantitative links between seemingly disparate fields such as protein biophysics, social science and music. [1] M.J. Buehler, "Tu(r)ning weakness to strength," Nano Today, Vol. 5 , pp. 379-383, 2010[2] S. Keten, Z. Xu, B. Ihle, M.J. Buehler, "Nanoconfinement controls stiffness, strength and mechanical toughness of beta-sheet crystals in silk," Nature Materials, Vol. 9, pp. 359-367, 2010[3] T. Knowles, M.J. Buehler , "Nanomechanics of functional and pathological amyloid materials," Nature Nanotechnology, Vol. 6(7), 2011
12:45 PM - MM8.10
Design and Development of Bio-Nanocomposites with Tunable Mechanical Properties and Control Adhesion, Proliferation and Differentiation of Human Mesenchymal Stem Cells.
Akhilesh Gaharwar 1 , Vipuil Kishore 1 , Christian Rivera 1 , Whitney Pavalko 1 , Chia-Jung Wu 1 , Ozan Akkus 1 , Gudrun Schmidt 1
1 Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana, United States
Show AbstractBioactive nanomaterials are currently the development focus of advance biomaterials for emerging technologies such as scaffolding, tissue regeneration, and controlled drug delivery. There is a tremendous need for new biomaterials that not only withstand the in-vivo mechanical forces but also facilitate the formation of functional tissues. A nanocomposites approach can be used to fabricate high-performance biomaterials with tailored physical, and chemical properties. However, much of the literature in this area has focused on reinforcing polymers with nanoparticles and little has been reported on the biological constraints that are biomedically relevant. Here we show that bio-nanocomposite formulations with defined cellular properties can be generated by inclusion of charged silicate nanoparticles as physical cross-linkers. The mechanical and biological properties of silicate cross-linked poly(ethylene oxide) (PEO) nanocomposites are evaluated. Rheological experiments were performed to determine the effect of silicate on the rigidity and stability of a physically cross-linked hydrogel network. A strong correlation has been established between silicate concentration and mechanical properties of nanocomposites. The dried nanocomposites containing high amount of silicate show hierarchical structure from micrometer to nanometer length scale, whereas no ordered arrangement is observed in nanocomposites containing low silicate concentration. In-vitro cell culture study indicates that silicate concentration play a vital role in adhesion and proliferation of human mesenchymal stem cells (hMSCs). The increase in silicate concentration significantly enhances attachment, spreading and proliferation of hMSCs. A well organized cytoskeleton is observed in hMSCs seeded on nanocomposite containing high silicate concentration. Quantitative reverse transcription polymerase chain reaction (RT-PCR) results showed an upregulation in the expression of osteocalcin on nanocomposites compared to the tissue culture polystyrene (TCPS) control. Together, these results suggest that silicate based nanocomposites are bioactive and have the potential to be used in a range of tissue engineering applications that require controlled cell adhesion and robust mechanical properties.
MM9:
Session Chairs
David Robinson
Mary Anne White
Thursday PM, December 01, 2011
Room 103 (Hynes)
2:30 PM - **MM9.1
Electrical Charge-Controlled Drug Delivery Using Nanoporous Metals.
David Robinson 1 , Timothy Martin 2 , Ryan Boehm 2 , Shaun Gittard 2 , Roger Narayan 2
1 Energy Nanomaterials, Sandia National Laboratories, Livermore, California, United States, 2 Biomedical Engineering, North Carolina State University, Raleigh, North Carolina, United States
Show AbstractNanoporous electrodes, such as those made from carbon or gold, can capture and release ionic analytes at concentrations near 1 mole per liter of pore volume through capacitive charging, ion exchange, or electrochemically reversible adsorption. In vitro studies suggest that this phenomenon can be the basis for a noninvasive, precise, and programmable drug delivery method. It eliminates the need for bulk fluid delivery to target tissue and requires only a thin electrical connection, minimizing pain and tissue disruption. Timing of release can be flexibly controlled. Compared to iontophoretic methods, there is minimal involvement of ions other than the drug, further reducing tissue disruption. We have designed effective gold electrode assemblies and observed the depletion and release phenomena using electrochemical methods and charged dyes. We are also evaluating use of nanoporous metal particles for intracellular delivery, triggered by changes in redox environment and ionic strength.
3:00 PM - **MM9.2
Electrospun Fibrous Biomedical Nanomaterials for Nanomedicine Applications.
Perena Gouma 1
1 , SUNY Stony Brook, Stony Brook, New York, United States
Show AbstractElectrospinning is a unique and versatile nano-manufacturing process capable of producing nanofibrous polymers and their composites. A versatile “bottom-up” technique, it has become already a high profile tool to synthesize hybrid nanocomposites, whether these are combinations of different polymers, polymer-ceramic, or polymer-metal systems in nanowire, nanobelt, or 3D nanofiber mat configurations. Furthermore, electrospun nanofibers are known to be excellent substrates for enzyme immobilization. The author’s group was the first to demonstrate a bio-nano-device (a urea biosensor) by urease immobilization in a polymer mat in a single step process. It has also pioneered the synthesis of pure single crystal ceramic (metal oxide) nanowires of “extreme” aspect-ratio used as biosensing probes by means of this method alone; as well as the construction of complex, porous, 3D architectures of natural polymers mimicking the bio-scaffold, i.e. the ExtraCellular Matrix (ECM) topography. The latter is considered a breakthrough for tissue engineering nanomanufacturing. Thus, electrospun nanofibers of hybrid materials are a class of bio-nano-composites that allow for versatile design, ease of manufacturing, and diversity of biomedical applications. Nanonedicine will eventually rely on electrospun nanofiber-based synthesis and processing to build active components in sensing, actuation, nanocues in templating, drug delivery systems, etc. This paper reviews the state-of-the-art, provides highlights from the author’s recent research in this field such as the ”band-aid”-type skin patch and nanowire-based breathanalyzer as disease diagnostics, and provides insights for the future of electrospun biomaterials.
3:45 PM - MM9.3
Microwave Synthesis of Superparamagnetic Maghemite Nanoparticles for Biomedical Applications: Effective Parameters on Their Characteristics.
Ahmet Ozenbas 1 , Ozge Baltaci 1
1 Metallurgical and Materials Engineering, Middle East Technical University, Ankara Turkey
Show AbstractIn this study production of fine particle Fe2O3 via microwave processing of Fe(NO3)3 . nH2O followed by low temperature annealing was reported. The samples were prepared at 5, 10, and 15 min microwave durations and heated in the furnace at 230°C for different periods. Maghemite phase (γ-Fe2O3) was observed for only 5 and 15 min samples without performing 230°C heat treatment. In the other samples both maghemite and hematite (α-Fe2O3) coexist. XRD was used to characterize the structural properties of nanoparticles. Approximate particle sizes were between 3-13 nm according to Scherrer’s equation. Multi point BET measurement results also show that samples have large surface area and they are nanometer sized particles. TEM study was conducted to examine the structure of the nanoparticles. The particle sizes obtained from the TEM images are in good agreement with the results obtained from Scherrer’s equation using XRD spectra. The TEM images of microwave processed samples indicate that average particle size is about 5 nm and the particles show a narrow size distribution which is an important parameter for biomedical applications. Magnetic measurements at different temperatures from 100 K to 350 K were performed with VSM (Vibrating Sample Magnetometer) in order to get information about magnetic properties of these nanoparticles. Zero-field cooled (ZFC) susceptibilities were measured by cooling the samples in zero magnetic field and then by increasing the temperature in an applied field of 100 Oe, while field-cooled (FC) curves were recorded by cooling the samples in an applied field of 100 Oe. Saturation magnetization values of these microwave processed samples were about 3.0 emu/g. From the VSM results it can be concluded that the samples containing only maghemite phase exhibited superparamagnetic behaviour, on the other hand samples containing both hematite and maghemite phases showed paramagnetic behaviour above 300 K, superparamagnetic behavior at lower temperatures.
4:00 PM - **MM9.4
Recent X-Ray Structure and Infrared Results for the Carbonate Ion in Hydroxyapatite.
Michael Fleet 1 , Xi Liu 2
1 Earth Sciences, University of Western Ontario, London, Ontario, Canada, 2 School of Earth and Space Science, Peking University, Beijing China
Show AbstractBiological apatite is carbonate-bearing hydroxyapatite (CHAP). Although the structural role of the carbonate ion in CHAP has a critical bearing on the growth and strength of bone, bone physiology, and the development of bone prostheses, detailed study has been frustrated by a number of factors, principally the nanoscale size of CHAP crystals in nature. In this study, relatively large crystals of CHAP have been synthesized inorganically at high temperature and pressure, and confirmed as appropriate analogue materials for biological CHAP using Fourier transform infrared (FTIR) spectroscopy. Single-crystal X-ray structure methods show that the type A carbonate ion is oriented in the structural channel of CHAP with two oxygen atoms close to the c-axis and the B carbonate ion is located near a sloping face of the substituted phosphate tetrahedron. FTIR spectra of CHAP are complex, particularly in the region of the asymmetric stretch (nu3) vibration. Nevertheless, we show that the relative intensity of the band for the out-of-plane bend (nu2) vibration varies linearly with the proportion of A and B carbonate determined independently from the X-ray structures. Close comparison of FTIR and X-ray structure results shows that a Na-bearing CHAP containing approximately equal amounts of A and B carbonate ions is a realistic model for the overall crystal structure of biological CHAP. However, whereas the hydroxyl ion is essentially ordered in the structure of synthetic CHAP, the absence of OH stretch and OH libration bands (near 631 cm-1) indicates that the OH content of biological CHAP is disordered in respect to its orientation and precise location both in the channel and elsewhere in the structure.
4:30 PM - **MM9.5
Morphological Control of Freeze-Cast Ceramics for Preparation of Hybrid Composites.
Mary Anne White 1 , Ran Chen 1 , Michel Johnson 1
1 , Dalhousie University, Halifax, Nova Scotia, Canada
Show AbstractPorous hybrid materials, combining the properties of organic and inorganic materials, have shown potential advantages such as toughness, high strength and low density, in many applications. A new type of porous hybrid Al2O3 ceramic was prepared by a freeze-casting process that produced a porous scaffold, followed by surface modifications with PMMA, yielding dense composite structures. We have utilized the organic-inorganic grafting technology in the interior structure of the porous ceramic to tailor the properties of hybrid materials.
5:00 PM - **MM9.6
New Developments in Electrodeposition of Organic-Inorganic Composites for Biomedical Applications.
Igor Zhitomirsky 1
1 , McMaster university, Hamilton, Ontario, Canada
Show AbstractElectrochemical methods have been developed for the deposition of nanocomposite films, containing natural biopolymers, inorganic nanoparticles, carbon nanotubes, drugs and proteins. Chitosan films were deposited by cathodic electrodeposition. Composite films containing hydroxyapatite, silica, titania and other bioceramics, bioglass in a chitosan matrix were obtained as monolayers, multilayers or materials of graded composition. Hydroxyapatite – chitosan films showed preferred orientation of hydroxyapatite nanoparticles in the chitosan matrix, similar to the orientation of hydroxyapatite in natural bones. The hydroxyapatite content in the films was varied in the range of 30-80 wt%. Multilayer films were obtained, containing organic and inorganic layers. The films exhibited good biocompatibility and provided corrosion protection of metallic implants in simulated body fluid solutions. It was found that heparin-chitosan films can be obtained using chitosan-heparin complexes. The addition of anionic heparin to cationic chitosan resulted in increasing cathodic deposition rate. Composite films showed improved biocompatibility. Bovine serum albumin – chitosan films were obtained by cathodic deposition. It was shown that this method allows electrodeposition of composite films containing other proteins and enzymes in a chitosan matrix for application in implants and biosensors.The feasibility of anodic deposition of alginic acid and hyaluronic acid has been demonstrated. Nanocomposite films containing hydroxyapatite and other bioceramics, bioglass were developed for the surface modification of biomedical implants. The method enabled the formation of uniform films of controlled composition on substrates of complex shape. Heparin was used as a model drug and bovine serum albumin was used as a model protein for the development of novel composites based on alginic acid and hyaluronic acid. The nanocomposites were obtained as monolayers, multilayers or materials of graded composition. New electrochemical methods offer the advantages of high deposition rate, the possibility of fabrication of uniform films on substrates of complex shape, rigid control of film microstructure and composition.
5:30 PM - **MM9.7
Dense Fibrillar Collagen Matrices: Mineralization, Properties and Implantation.
Nadine Nassif 1 , Yan Wang 1 , Marc Robin 1 , Jeremie Silvent 1 , Laure Bonhomme 1 , Anne Meddahi-Pelle 2 3 , Thierry Azaies 1 , Marie-Madeleine Giraud-Guille 1 , Florence Babonneau 1
1 , LCMCP, CNRS, UPMC, Collège de France, Paris France, 2 , INSERM U698, BPC, CHU Xavier Bichat, Paris France, 3 , UFR médicale de Paris Ile de France Ouest, Université Versailles Saint-Quentin en Yvelines, Paris France
Show AbstractMimicking bone is a tremendous challenge and the aim for many in the fields of materials science, tissue engineering and medicine. Bone tissue itself is a composite material which intimately associates its organic and mineral phases. Collagen type I molecules form fibrils, organized into fibers that further pack into regularly dense and ordered networks spanning over many length-scales. Furthermore, hydroxyapatite (HA) nanocrystals nucleate in gap regions of collagen fibrils in such way that their crystallographic c-axes are co-aligned with the long axes of the fibrils. These hierarchical structures give bone its characteristic biological and mechanical behaviours. Recent experiments have until now only been able to organize such structures up to the fibrillar level. The preparation of dense fibrillar collagen matrices through a sol/gel transition at variable concentrations offers routes to produce a range of simple, non toxic materials (1). Especially at high concentration, at least above 80 mg/mL, they show ultrastructures described in compact bone, namely liquid crystalline cholesteric geometries. In this presentation, an original process enabling reproduction of the three-dimensional collagen architecture, i.e. level 4 described in bone by Weiner and Wagner (2), and bone tissue mechanical anisotropy will be presented (3). This process is based on a “one-pot” co-precipitation method coupling the liquid-crystalline properties of collagen (4) to a bioinspired HA mineralization process that relies on acidic calcium phosphate precursors (5). Moreover, more recently a new process was set to get a fully homogeneous sample for an industrial upscaling. Homogeneous dense fibrillar collagen matrices were obtained at the fibril’s up to the cm scale (6).In parallel, in vitro and in vivo investigations were performed to control their cyto- and biocompatibility as well as evaluate their potentialities as bone repair.Our findings emphasize that physical and chemical interactions can lead to hierarchical structures of equal complexity as those found in biological materials and to novel strategies in synthesizing biomimetic materials opening new perspectives in regenerative medicine. 1.M.M. Giraud-Guille, C. Hélary, S. Vigier, N. Nassif, Soft Matter. 6, 4963-4967 (2010).2.S. Weiner, H.D. Wagner, Ann. Rev. Mater. Sci. 28, 271-298 (1998).3.N. Nassif, F. Martineau, O. Syzgantseva, F. Gobeaux, M. Willinger, T. Coradin, S. Cassaignon, T. Azaïs, M.M. Giraud-Guille, Chem. Mater. 22, 3653–3663 (2010).4.M.M. Giraud-Guille, Calcif. Tissue Int. 42, 167-180 (1988).5.N. Nassif, F. Gobeaux, J. Seto, E. Belamie, P. Davidson, P. Panine, G. Mosser, P. Fratzl, M.M. Giraud-Guille, Chem. Mater. 22, 3307–3309 (2010).6.M.M. Giraud-Guille, N. Nassif, Y. Wang, A. Pellé, C. Hélary, French Patent n°10/54194; Y. Wang, J. Silvent, M. Robin, F. Babonneau, A. Meddahi-Pellé, N. Nassif , M.M. Giraud-Guille, submitted.
MM10: Poster Session
Session Chairs
Vipul Dave
Sungho Jin
Roger Narayan
Seeram Ramakrishna
Donglu Shi
Friday AM, December 02, 2011
Exhibition Hall C (Hynes)
9:00 PM - MM10.1
Synthesis, Characterization, and Bioavailability Evaluation of Biocompatible Nanoclay Intercalated with Glutathione for Antioxidant Delivery.
Miri Baek 1 , Soo-Jin Choi 1
1 , Seoul women's university, Seoul Korea (the Republic of)
Show AbstractA ubiquitous tripeptide, glutathione (GSH), plays an important role in detoxification, activation of immune system, intermediary metabolism, transport, and protection of cells against free radicals or reactive oxygen species. However, orally administered GSH can be easily degradable to free amino acids by chemical and enzymatic hydrolysis, resulting in low absorption into the blood circulation and low bioavailability in the tissue. In this study, we intercalated GSH into cationic nanoclay delivery carriers, montmorillonite (MMT), to improve GSH bioavailability in biological system. The hybrid was also coated with positively charged polymer for better stability in gastrointestinal tract, and then characterized by powder X-ray diffraction, fourier transformed infrared, and thermogravimetric analysis. The result shows that GSH was successfully intercalated into the interlayer spaces of MMT. The hybrid had similar antioxidant activity to free GSH in vitro as measured by DPPH and ABTS radical scavenging assays, and more remarkable antioxidant activity was found in the plasma orally administered with the coated hybrid in vivo. Pharmacokinetic study of the hybrid systems showed significantly long circulation time and high absorption rate compared with free GSH in mice. Moreover, GSH content in the liver considerably increased after oral administration of both the hybrids, suggesting their delivery efficiency. Acute oral toxicity test demonstrated that the hybrid systems did not cause any abnormal changes in terms of body weight, behavior, and mortality. All the results suggest that the present MMT intercalated with GSH has great potential to enhance bioavailability of GSH in vivo.
9:00 PM - MM10.10
Preparation of Boron Carbide Nanoparticles for Boron Neutron Capture Therapy Agent by Pulsed Laser Melting in Liquid.
Yoshie Ishikawa 1 , Naoto Koshizaki 2 , Qi Feng 1
1 Department of Advanced Materials Science, Faculty of Engineering, Kagawa University, Takamatsu Japan, 2 Physical Nano Process Group, Nanosystem Research Institute (NRI), National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba Japan
Show AbstractBoron is a useful element for neutron capture therapy due to the high neutron absorption cross-section. The boron neutron capture therapy (BNCT) is based on tumor destruction by α-particles produced from nuclear division of 10B. If 10B is selectively introduced within the tumor cells, the BNCT can destroy only tumor cells due to the 10-μm short travelling distance of released α-particle equivalent to the size of tumor cells. p-boronophenylalanine (BPA) and mercaptoundecahydrododecaborate (BSH) are clinically used for BNCT, whereas these compounds contain small number of B atoms. Since highly concentrated B in tumor cell is imperative for effective therapy, enormous dose of BPA and BSH is necessary and impose strain on a patient. Boron carbide nanoparticles are an attractive alternative for BNCT agent, because of high concentration of boron atoms and its inertness against oxidation.In this study, we attempt to fabricate boron carbide particles for BNCT by pulsed laser melting of B particles in liquid phase. The advantages of this technique are the highly pure particulate production without the use of surfactant and simple fabrication process of nanoparticles.Raw B powders from 50 to 100 nm in diameter were dispersed in ethanol, and irradiated with the second harmonic of Nd:YAG laser operated at 10 Hz with pulse width of 7 ns with various fluences. Submicron spheres B4C from 50 to 400 nm in diameter were dominantly formed when the laser fluence from 0.4 to 1.5 J cm-2 pulse-1. The obvious shape change and size increase of particles by laser irradiation suggested that the raw B grains were melted by laser heating. C species, which were formed by decomposition of solvent molecules surrounding the B droplets, were dissolved into the B droplet. Then the spherical particles including B4C crystals formed via cooling process of the droplets. In contrast, H3BO3 formation occurred by laser irradiation with the fluence higher than 1.5 J cm-2 pulse-1 because of an explosive ejection of active B species due to ablation.According to HRTEM observation, the B4C spheres obtained by this technique were encapsulated by graphite. This is beneficial for a further surface modification of the particles toward biomedical functionalization. Thus, the B4C particles obtained by this technique have a possibility for BNCT application.
9:00 PM - MM10.11
Physicochemical Properties of Fish Scale Collagen and Chitosan Nanocomposites.
Marie Yamamoto 1 , Tomohiko Yoshioka 1 , Toshiyuki Ikoma 1 , Junzo Tanaka 1
1 Department of Metallurgy and Ceramics Science, Tokyo Institute of Technology, tokyo Japan
Show Abstract Collagen is the most abundant structural protein found in the animal body. Because of its good biocompatibility and moderate biodegradability, type one collagen has been widely used as a biomedical material. There are some problems to be solved: for example, collagen extracted from skin of bovine and porcine has a potential risk of common virus to human being and the mechanical strength is not enough for handling in operations. To achieve a superior biomedical material, we have focused on a fish scale collagen with the similar denaturation temperature of porcine collagen, which has no zoonotic infection. Moreover, to improve the mechanical property, the nanocomposites of fish scale collagen and chitosan with different charges have been fabricated. In this study, the novel collagen and chitosan nanocomposites were prepared by mixing them under moderate pH conditions to control the interfacial interaction of their functional group. The structural and viscoelastic properties of nanocomposites as well as denaturation temperatures were elucidated to design scaffolds for tissue engineering. Tilapia fish scale atelocollagen and chitosan solution were mixed at pH5.4, and carbonate-bicarbonate buffers with different pH values were added into the mixed solution to adjust pH. The mixtures were then incubated at 28degree celsius for 3 hours. The biscoelastic property of the gels obtained was analyzed at room temperature. The nano composite gels were further freeze-dried after completely exchanged with solvent of ethanol-series and t-butyl alcohol. The surface morphology of the freeze-dried samples was observed with a scanning electron microscope (SEM). The freeze-dried samples were rehydrated by soaking into Dulbecco’s phosphate buffered saline and the moist samples were analyzed by a differential scanning calorimeter(DSC). The SEM observation shows that the fibrous structures were found in the freeze-dried nanocomposites prepared ath the pH range of 6.5 to 9.0, and were quite similar to the fibril shape of a pure collagen. The DSC analysis exhibited denaturation temperature of collagen in the nanocomposites was 49degree celsius whicha was comparatively higher than that of pure collagen . The elasticity(G’) of the composites was entirely higher than that of pure collagen gel. Themaximum G’ value was 1830±5.0 Pa for the nanocomposites prepared at pH6.5 which was 11times higher than that(170±2 Pa) of the pure collagen . It clearly indicated that the moderate pHvalue at 6.5 in the mixture induced the strong interfacial interaction of collagen and chitosan at molecular levels. These results suggested that the novel collagen-chitosan nanocomposites have suitable properties of a scaffold for tissue engineering.
9:00 PM - MM10.12
In Situ Mineralization of Hydroxyapatite Using Amino Acid Modified Clay for Bone Tissue Engineering.
Avinash Ambre 1 , Dinesh Katti 1 , Kalpana Katti 1
1 Civil Engineering, North Dakota State University, Fargo, North Dakota, United States
Show AbstractNanoclays have been extensively investigated in literature as components of nanocomposites with polymers to enhance mechanical, barrier and other properties of the polymers. Here we report a unique application of nanoclays in scaffolds with biopolymers and synthetic polymers. In addition, the osteoconductive nature of hydroxyapatite has made it an important component of scaffold materials for bone tissue regeneration. Taking cues from biomineralization, insitu hydroxyapatite clay (montmorillonite- MMT) was synthesized using 5-aminovaleric acid (unnatural amino acid) modified MMT. Fourier Transform Infrared (FTIR) spectroscopy studies indicated that the carboxylic groups of 5-aminovaleric acid had a role in the formation of hydroxyapatite (HAP) in modified clay. The insitu HAPclay was used for the preparation of biopolymer/insitu HAPclay and synthetic polymer (polycaprolactone)/insitu HAPclay scaffolds and also with biopolymer system chitosan-polygalactouronic acid. The proliferation and differentiation of human mesenchymal stem cells (hMSCs) was studied on these scaffolds through cell culture assays to assess their potential for bone formation. The insitu HAPclay significantly improve mechanical properties of the fabricated polymer scaffolds as well as enhancing the biological responses as evaluated through compatibility assays. The use of MMT clay modified with unnatural amino acids and insitu HAPclay to develop scaffold materials intended for bone tissue regeneration are some of the important contributions of this work.
9:00 PM - MM10.13
Autonomic Healing of Acrylic Bone Cement.
Amelia Gladman 1 2 , Brian Steinberg 2 3 , Meagan Wettengel 2 3 , Jeffrey Moore 2 3 , Nancy Sottos 1 2 , Scott White 1 2 4
1 Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States, 2 Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States, 3 Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States, 4 Aerospace Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States
Show AbstractOver the last 50 years, poly(methyl methacrylate) (PMMA)-based bone cement has become the principal biomaterial for use in fixation during orthopedic joint replacement surgeries. These surgeries affect a large population, with over 200,000 reported total hip replacements and over 500,000 total knee replacements performed in 2007 in the United States alone [1]. Despite its long history of use, there are significant problems associated with acrylic bone cement, including fatigue failure of the cement, which can lead to aseptic loosening and revision surgeries for patients [2]. To extend the lifetime of bone cement we have developed a self-healing cement using a microencapsulated free radical-based healing chemistry. Healing is accomplished by dispersing two types of polymeric microcapsules – one that contains acrylate monomers and a tertiary amine activator in solvent, and another with a peroxide initiator dissolved in solvent – in a commercial bone cement matrix. Upon crack propagation, the microcapsules rupture and release the healing components into the crack plane, and free radical-based polymerization bonds the crack closed. Fracture tests are conducted using tapered double cantilever beam (TDCB) test specimens at a variety of capsule concentrations. Both virgin and healed fracture toughness is measured at room temperature and body temperature. References: 1. Impatient Surgery. www.cdc.gov/nchs/fastats/insurg.htm: Centers for Disease Control and Prevention- National Center of Health Statistics; 2011.2. Hip Joint Replacement. www.nlm.nih.gov: United States National Library of Medicine; 2010.
9:00 PM - MM10.14
Pull-Spinning: A Rapid Prototyping of Nano-Scale Fibrous Assemblies.
Mohammad Badrossamay 1 , Josue Goss 1 , Kevin Parker 1
1 Disease Biophysics Group, Wyss Institute for Biologically-Inspired Engineering, School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts, United States
Show AbstractPolymeric nanofiber structures have been widely used in a variety of applications from tissue engineering to micro-electronics due to their high surface area to mass ratios and high porosities [1, 2]. In electrospinning, a commonly used nanofiber formation technique, low production rates and required high voltage electric fields persuade researchers to explore new technique of nanofiber formation [3, 4]. We have developed a facile technique of nanofiber formation termed Pull-Spinning. In pull-spinning a rotating blade is dipped into a polymer solution or melt to pull out the polymer liquid and projecting polymeric fibers onto a stationary collector. Pull-spinning is a cost effective, versatile, and high-throughput technique which produces fibers with diameter ranging from micro to nanometer (≤50 nm) size from a very small droplet of polymeric liquids or continuous flow of polymer liquid. We have fabricated nano-scale structures of biodegradable polylactic acid (PLA) polymer and hydrophilic polyethylene oxide (PEO) polymer. In pull-spinning, the tips of a rotating blade are dipped into a liquid polymer solution. Using capillary forces, the polymer adheres to the protrusions on the blade and is pulled from the bulk solution at high angular speeds. Nanometer size fibers are formed due to jet necking and solvent evaporation as it travels to the collector. The morphology of the produced fibers can be changed by altering the geometry of the blade, viscosity of the polymer solution, volatility of the solvent and the distance between the blade and collector. Pull-spinning fabrication technique is quite unique and that the potential applications of the technology are widespread and it overcomes many limitations of common nanofiber formation techniques.References:1.Madurantakam , P.A., et. al , Nanomedicine, 2009, 4 (2), 193-206.2.Liao, Y., et. al, Nano Letters, 2011, 11(3), 954-959.3.Badrossamay, M.R., et al., Nano Letters, 2010, 10(6), 2257-2261.4.Senthilram, T. et. al, Materials Today, 2011, 14(5), 226-229.
9:00 PM - MM10.15
Protein Behavior under Confined Environments and Negatively Curved Nanointerfaces.
Xi Qian 1 2 , Jonathan Dordick 1 2 3 , Richard Siegel 1 2
1 Rensselaer Nanotechnology Center, Rensselaer Polytechnic Institute, Troy, New York, United States, 2 Department of Materials Science and Engineering, Rensselaer Polytechnic Institute, Troy, New York, United States, 3 Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, New York, United States
Show AbstractThe development of nanotechnology for biomedical applications has provided both the ability and incentive to study interactions between nanostructures and biomolecules (e.g., proteins and peptides). While the scale of the contacting surface is comparable to the size of a folded protein, the specific geometry of the interacting nanoscale surface will influence the manner of contact between proteins and material substrates, potentially altering the protein’s behavior. For example, nanostructures possessing negative curvature could enable encapsulation of adsorbed proteins, and thus allow a unique opportunity to explore the effect of large nanoscale contact area, as well as bio-mimic molecular crowded environment, on protein behavior. However, despite this opportunity, such nano-bio interactions have not been widely explored. To ameliorate this lack of information, not only a more precise bimolecular characterization of absorbed proteins is required, but also enhanced nanoscale synthesis and modification of such nanostructures is critical. In our current work, we are developing a new form of nano-bio conjugates in which proteins are encapsulated, taking advantage of a previously reported method for creating gold nanocages, to study protein behavior in such an environment. The hollowed gold nanocage is synthesized via galvanization with silver nanocube precursors, and chemically modified on both interior and exterior surfaces for biocompatibility, as characterized via X-ray photoelectron spectroscopy. Precise morphology controls are involved in the synthesis and yield highly mono-dispersed 50 nm cubic gold nanocages with pore sizes about 10 nm on the surface, which has been confirmed via electron microscopy (SEM, TEM) and X-ray/electron diffraction. Enzymatic proteins such as lysozyme and alpha-chymotrypsin are involved in the nano-bio conjugates. Characterization methods including UV, circular dichroism, surface-enhanced Raman spectroscopies, and enzymatic activity assays are applied to measure protein absorption, conformational change, and enzymatic activity, which are three key properties that are being considered in exploring such nano-bio interactions. Since negative curvature and confined space often co-exist as material substrate features, it is essential to look at the combined effects of both features. The present study is designed to expand our fundamental understanding of nano-bio interactions, and thus help to further develop biomedical applications of nanomaterials.This work was supported by the US National Science Foundation under Grant No. DMR-0642573.
9:00 PM - MM10.16
The Effects of Gold Nanoparticles on the Stability and Non-Linear Response of Microbubbles.
Graciela Mohamedi 1 , Mehrdad Azmin 1 , Eleanor Stride 1 , Mohan Edirisinghe 1 , Luis Liz-Marzan 2 , Isabel Pastoriza-Santos 2 , Jorge Juste 2
1 , University College London, London United Kingdom, 2 Departamnto de Quimica Fisica, Universidade de Vigo , Vigo Spain
Show AbstractPhospholipid coated microbubbles are widely used as contrast agents(UCA) in medical ultrasound imaging, due to their non-linear response to acoustic excitation. Controlling the stability of microbubbles in vivo over the course of a typical examination, however, represents a considerable challenge especially at the relatively high intensities required to generate significantly non-linear signals. This poses a barrier to the use of contrast agents particularly in quantitative imaging and therapeutic applications. The aim of this study was to investigate the potential for stabilising microbubbles using solid nanoparticles adsorbed onto their surfaces. A new theoretical model was developed to describe the influence of interfacially adsorbed solid particles upon the dissolution of a gas bubble in a liquid. The results indicate that the presence of the nanoparticles would inhibit gas diffusion and the tendency to undergo Ostwald ripening, thus increasing the life span of the bubbles. The experimental results confirm the theoretical predictions: near monodisperse microbubbles prepared using a microfluidic device with a surface coating of phospholipid, surfactant and 15 nm ± 10% gold nanoparticles underwent negligible changes in their size and size distribution over a period of 30 days at ambient temperature and pressure. Under the same conditions,bubbles coated with the same surfactant but no nanoparticles survived only a matter of hours. In addition to increasing their stability, the presence of the nanoparticles was also found to enhance the non-linear behaviour of the bubble at low acoustic pressures and this is under further investigation.
9:00 PM - MM10.17
Oxide Nanowires for Neuron Adhesion and Growth.
Emanuela Gobbi 1 2 , Guido Faglia 1 , Elisabetta Comini 1 , Matteo Ferroni 1 , Andrea Ponzoni 1 , Giorgio Sberveglieri 1 , Federica Bono 3 , Cristina Missale 3 , Ginetta Collo 3
1 SENSOR Laboratory, Dept. of Chemistry and Physics for Materials Engineering , University of Brescia & IDASC-CNR , Brescia Italy, 2 Dept. of Environmental and Agricultural Sciences, University of Udine, Udine Italy, 3 Dept. of Biomedical Sciences and Biotechnologies, Division of Pharmacology, University of Brescia, Brescia Italy
Show AbstractHigh-yield stem cell differentiation into neurons coupled with in vitro methodological improvements to study pharmacologic agents could result in possible large-scale industrial implementation providing that appropriate material to build the cell culture infrastructure is available. Cells in their natural environment interact with components in the nanometer scale, suggesting a crucial role of the nanoscale surface in regulating adhesion, growth and differentiation.In this study, novel nanopatterned oxide materials were developed, with specific tailored properties optimized for the in vitro adhesion and growth of neural cell types. SnO2 nanowires (NWs) were deposited with Vapour-Phase and Vapour-Liquid-Phase growth mechanism (Au and Pt were used as catalysts). Experimental parameters for optimal NWs production on glass substrates were thoroughly addressed. The materials were comprehensively characterized by Scanning Electron Microscopy (SEM) and Atomic Force Microscopy (AFM).In vitro cell culture studies to investigate the attachment of the cells on the modified surfaces are presented. Striatal cells from mouse embryos were grown on Au or Pt SnO2 NWs and on control samples. Control samples, glass coverslides and cell culture plastic plates were coated with poly-D-lisine and laminine. The various nanomaterials did not undergo to any coating.Twenty four hours after plating on nanomaterials and control samples striatal cells showed clear signs of adhesion to the Au SnO2 NWs. Four days after plating, striatal cells were still adherent and showed a typical differentiation into a neuronal morphology, with neurites extending for long distances. At simple microscopic observation their morphology was similar to that of striatal neurons plated on standard substrates. We also noted that striatal cells plated on the Au SnO2 NWs did not differentiate into astrocytes at variance with cells plated on glass cover slides, tissue culture plates or Pt SnO2 NWs. The absence of astrocytes on the Au SnO2 NWs suggests that this new substrate may represent a breakthrough for the development of pure neuronal cell cultures to study the direct effects of pharmacological compounds. In conclusion, we have shown that Au SnO2 NWs could be a suitable substrate for adhesion, survival and differentiation of striatal cells into a neuronal phenotype.
9:00 PM - MM10.18
Practical Considerations for Medical Applications Using Biological Grafts and Their Derivatives.
Shayanti Mukherjee 1 2 , Jayarama Reddy Venugopal 2 , Rajeswari Ravichandran 2 3 , Santosh Mathapati 4 5 , Soma Guhathakurta 4 , Michael Raghunath 1 6 , Seeram Ramakrishna 2 3 7
1 Division of Bioengineering, National university of singapore, Singapore Singapore, 2 Nanoscience and Nanotechnology Initiative, National University of Singapore, Singapore Singapore, 3 Department of Mechanical Engineering, National University of Singapore, Singapore Singapore, 4 Frontier Tissueline, Frontier Lifeline & Dr. K.MCherian Heart Foundation, Chennai India, 5 , Indian Institute of Technology, Chennai India, 6 Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore Singapore, 7 Institute of Materials Research and Engineering, a-star, Singapore Singapore
Show AbstractThe art and science of using biological tissue grafts from animal and human sources for various ailments is nascent. Various research groups around the world are actively investigating the potential prostheses of biological origin using several methods of processing and fabrication before they can be used for the specific application. As the biological graft is rendered a cellular, it offers a scaffolding framework for host cellular repopulation and revascularization. Residual cellular components in a bioprosthetic material are known to give rise to undesired effects, such as calcification and immunological recognition, which necessitates effective decellularization processes. Decellularization methods such as glutaraldehyde, polyepoxide cross-linking treatments and dye-mediated photooxidation have allowed removal of antigenic materials in the tissue while maintaining the natural mechanical properties of graft. The therapeutic capabilities of treated tissues have been investigated with regard to various organ complications such as for trachea, abdominal wall, heart valves, nerves, liver as well as skin. Naturally derived biological scaffolds offer many mechanical, chemical and biological advantages over synthetic materials, and thus hold tremendous potential for use in tissue engineering therapies. Owing to these advantages, the rationale of using decellularized biological grafts is given considerable importance. This review article focuses on the preparation of biological grafts in its usable form and its application in various clinical settings. It also discusses the trends in the tissue engineering advances and the important ethical considerations in the development of such natural tissues in various clinical applications.
9:00 PM - MM10.19
Synthesis of Core-Shell Biopolymer Particles Using Coaxial Electrospray.
Choi Hui Lim 1 , Michael Mullins 1
1 Chemical Engineering, Michigan Technological University, Houghton, Michigan, United States
Show AbstractCore/shell poly-L-lactic acid (PLLA) microparticles were fabricated via electrospraying, utilizing a novel, modified coaxial nozzle design. These particles were synthesized with different components in the core/shell layers that represent three classes of systems of interest for drug delivery applications: aqueous phase/PLLA, PLLA/PEG, and oleic acid/PLLA. The binary components were characterized for their physical properties and interfacial energies, and these factors were related to the final core/shell particle properties and the optimal electrospraying parameters. A systematic study of the coaxial nozzle design and the operating conditions for these binary systems was also conducted, and some simple scaling laws developed. High-speed, high-resolution video of the nozzle during spraying was used to refine the nozzle design, and evaluate the best processing conditions. To evaluate the particle morphology and size distribution, both electron and optical microscopy were employed. However, since these techniques do not directly assess the shell structure, each phase was doped with a different colored fluorescent dye to aid in the measurement of the core/shell size ratio via fluorescence microscopy. The key factors in determining the shell thickness and core size included: the interfacial tension of the core and shell phases, the electrical properties of each phase, and the uniformity of flow of each phase from the coaxial nozzle.
9:00 PM - MM10.2
Antibody-Based Aggregation of Blood Cells for Plasma Harvest.
Yo Han Choi 1 , Kwang Hyo Chung 1 , Jung Hoon Shin 2 , Gun Young Sung 1
1 , Electronics and Telecommunications Research Institute, Daejeon Korea (the Republic of), 2 , Korea Advanced Institute of Science and Technology, Daejeon Korea (the Republic of)
Show AbstractIt is very important to gather plasma from whole blood for diagnostic purposes. We describe herein a rapid method for the separation of plasma from blood cells without any power supply.Blood cellular parts including red blood cells and white blood cells occupy about 45 % of blood volume. In order to conduct most of diagnostic assays, these cellular components must be removed to reduce colorimetric background or enzymatic noises. Centrifugal sedimentation has been the popular method only if there are available facilities with electrical power. Mechanical filtration during lateral permeation through fabric matrices such as filter paper is another substitutional method adopted by disposable rapid diagnostic kits which are devised for situations without centrifugal facilities. However it takes long time to remove cellular components by simple filtration method. We introduced polyclonal antibody which captures blood cells to make cellular aggregate, which accelerates the sedimentation of blood cells even in undiluted whole blood.Two C57BL/6 mice were used to generate anti-human whole blood polyclonal antibody. 10 ul of human whole blood was washed with saline buffer at least 3 times to remove plasma components. The washed blood cells were fixed with formaldehyde/glutaraldehyde to prevent them from rapid rupture after immunizations. Mice were sacrificed for bleeding after 6 times of intraperitoneal immunization with 3 week interval. Two separate sera were harvested from the bloods by centrifugation, and the aggregation of human blood cells by these sera was confirmed. 40 ul of undiluted human blood cells made evident aggregate when they were mixed with 4 to 8 ul of anti-human whole blood serum. The aggregation could be clearly detected through an inverted light microscope as well as naked eyes. The formation of aggregate was an instantaneous phenomenon which needed no incubation time. There was no detectable aggregate when whole blood was mixed with negative control serum which had been derived from a mouse without immunization. We fabricated a simple plastic chip to measure the sedimentation speed of blood cells. Undiluted human whole blood with anti-blood serum showed faster sedimentation of blood cells compared with the one with negative control serum. The sedimentation speed increased at least 5 times. The accelerated sedimentation of blood cells by aggregation would be the promising technical upgrade for the pretreatment of whole blood in point-of-care diagnostics. Purification of specific antibodies and dimer formation using protein A would improve the practical potential of these blood-capturing antibodies.
9:00 PM - MM10.20
Mechanical Conditioning of PLGA Nanofiber Alignment for Implantable Devices.
Fabienne Meier 1 , Dong Han 2 , Frank Ko 3 , Karen Cheung 2
1 School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne Switzerland, 2 Electrical and Computer Engineering, The University of British Columbia, Vancouver, British Columbia, Canada, 3 Advanced Materials and Process Engineering Laboratory, The University of British Columbia, Vancouver, British Columbia, Canada
Show AbstractMats of aligned electrospun poly(lactic-co-glycolic acid) (PLGA) nanofibers shrink (-40%) and fibres lose alignment when incubated at 37°C in PBS that mimics the in vivo environment. This degradation behaviour is undesirable in applications such as nanofiber structures to guide axon regeneration. We present a novel stretch-drawing process to preserve the original nanofiber morphology after implantation. The alignment of the nanofibers in the mat is maintained through a stretching process, in which a tensile force is applied by springs in the direction parallel to the alignment. Mats are first incubated under tension to stretch the fibers, then without tension to confirm that the alignment will remain after implantation.The extent of fibre alignment is analyzed using ImageJ which gives a distribution of fiber orientation for each image (using OrientationJ plugin written by D. Sage). The full-width at half-maximum (FWHM) for each distribution is calculated in Matlab. The initial alignment distribution is ± 7° from the prevailing angle. However, after 2 days of incubation (without stretching), this value rises to ± 103°. Instead, when the mat is incubated with stretching for 3 days, the alignment distribution is ± 6°. After two further days of degradation without stretching, the fiber alignment is preserved (p-value: 0.04) if the mat is previously incubated under tension. The alignment remains even after the removal of the tension (mimicking in vivo conditions): ± 7°. Shrinkage and fiber alignment are highly correlated (Pearson correlation of -0.94).The shrinkage force in the mat during incubation is expressed in terms of the specific stress of the fibre mat: Specific stress = (tensile stress of the springs) / ((mass) * (surface area of the sample)). Two springs with different elastic constants have been used to test the setup (k1 = 6337 kPa, k2 = 884 kPa). Using k1, the mat shrinks -6% of its initial length and counter a 121 kPa /(g cm^2) stress. Using k2, the mat shrinks -25% and it creates a stress greater than 44 kPa /(g cm^2). The force of the mats is actually higher than the spring's force as they shrink and do not stay in their initial position. As a control, fixing the mats at their initial dimension induces a drastic decrease of their strength.Ongoing work includes determining the changes of thermal properties, such as glass transition temperature, and thermally induced crystallization as a function of time during the course of degradation process.
9:00 PM - MM10.22
A Novel Injectable Colloidal Nanogel with Extremely High Water Content for Drug Delivery.
Meng-Hsuan Hsiao 1 , Dean Mo Liu 2
1 , National Chiao Tung University, Hsinchu Taiwan, 2 , National Chiao Tung University, Hsinchu Taiwan
Show AbstractIn previous study, native chitosan was successfully modified into amphiphilic chitosan by grafting hydrophilic group (Carboxymethyl) hydrophobic group (hexaonyl) onto the main chain of chitosan, Carboxymethyl-hexaonyl chitosan (CHC). CHC polymer formed double-layer nanocapsule in aqueous environment and be able to carry drug or protein molecular in hollow part or mesosphere of shell. In our study, we neutralize the positive charge on CHC particle surface by using negative salt (β-glycerophosphate) to fabricate an injectable nanogel that is thermo-induced gelation (CHC nanogel). As temperature increasing, the rate of sol-to-gel of CHC nanogel is also highly raising, so CHC nanogel can be design as an injectable drug delivery system. Moreover, the most part of formula for CHC nanogel is constituted by water (more than 97%), gelation occur even with less than 1% CHC nanoparticle. Subsequent application of CHC nanogel is to carry drugs of various degree toward water affinity (from water soluble, ethosuximide (ESM), to water insoluble, camptothecin (CPT)), and the controlled drug release behavior in vitro has been systematically incestigated. The experimental results indicated that the CHC anogel is a long-term, sustained release profile for both types of drugs were monitored and release kinetics suggested a two-stage profile, suggesting a bimodal release attern, and has been confirmed to be a result of drug distribution, i.e, within the nanocapsules and inter-capsule regions. Besides, CHC nanogel is hybridize with magnetic nanoparticle or other components to design as a controllable drug delivery system which is able trigger by high frequency magnetic field (HFMF) or ultrasound. Biocompatibility, Sol-to-gel transition, nanostructure, and biocompatibility of the nanogel were characterized, and was considered as a novel water-borne drug delivery system.
9:00 PM - MM10.23
Designing Polysacchride-Polyeletrolyte Core-Shell Nanoparticle with Combined Functionalities as Dual-Drug Delivery System.
Fu-Hsuan Chou 1 , Chun-Yu Chang 1 , Charles Yen 2 , Wei-Yang Hong 1 , Dean-Mo Liu 1
1 Department of Materials Science and Engineering, National Chiao Tung University, Hsinchu Taiwan, 2 Department of Biotechnology, University of British Columbia, Vancouver, British Columbia, Canada
Show AbstractCombined therapy has been clinically well-recognized as effective in treating many diseases, including tuberculosis, leprosy, cancer, malaria, and HIV/AIDS, by which two or more medications were designed to treat a single disease. Conventional single-dose drug delivery systems performed one designed drug elution pattern at a time and could hardly fulfill the need of combined therapy, unless multiple administrations applied. Although a few of reports have been highlighted the clinical importance of multiple drug delivery systems, e.g., liposomal nanoparticles, it is more interesting if functions such as multiple drugs of diverse physico-chemical properties, imaging, and/or targeting modalities can be technically integrated into a single biocompatible nanocarrier. In this work, a core-shell nanoparticle was prepared using an amphiphilic chitosan which can be self-assembled into a nanocapsule as a core, followed by electrostatic coating with a number of functional layers, as the shell, of opposed charges. Drugs with various characters can be encapsulated in either core or shell region, and a variety of drug release patterns can be designed as needed. Such a core-shell multifunctional nanocarrier with a size of ~200 nm was prepared with docetaxel (water-insoluble substance) and doxorubicin (water-soluble) encapsulated in the core and shell region, respectively. A dual drug release profile can be selectively tuned from burst-like to sustain release pattern via the thickness and charging potential of the shell layer. A further integration using ionic fluorescence molecule deposited on the core-shell nanocarrier permitted a molecular imaging modality to be equipped in this nanocarrier. Excellent cytocompatibility and efficient cellular internalization of the resulting multifunctional dual-drug delivery system visualized its medical potential for advanced nanotherapeutic applications.
9:00 PM - MM10.24
Fully Biodegradable Antioxidant Copolyoxalate Nanoparticles for the Treatment of Inflammatory Diseases.
On Hwang 1 , Iljae Lee 1 , Hyungsuk Lim 1 , Gilson Khang 2 , Dongwon Lee 2 1
1 Department of BIN Fusion Technology, Chonbuk National University, Jeonju, Chonbuk, Korea (the Republic of), 2 Department of Polymer/Nano Science and Technology, Chonbuk National University, Jeonju, Chonbuk, Korea (the Republic of)
Show Abstractp-Hydroxybenzyl alcohol (HBA) is one of phenolic compounds from Gastrodia elata which has been widely used herbal agents for the treatment of headache, tetanus and inflammatory diseases for several centuries in Oriental countries. HBA plays a pivotal role in protection against oxidative damage-related diseases due to anti-oxidant effects. We have developed biodegradable copolyoxalate in which HBA is chemically incorporated into its backbone. The HBA-incorporated copolyoxalate (HPOX) was synthesized from a one step reaction of oxalyl chloride, 1,4-cyclohexamethanol and HBA. In design, the copolymers degrade by hydrolysis and release HBA, antioxidant and anti-inflammatory agent. The copolymers had a molecular weight of 15,000 Da and were hydrophobic to formulate into nanoparticles with a mean size of 400 nm. The Amplex Red assay revealed that the HPOX nanoparticles had an ability to scavenge hydrogen peroxide. The nanoparticles also reduced the generation of hydrogen peroxide in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells in a dose-dependent manner. Flow cytometry and fluorescence imaging further confirmed that HPOX nanoparticles scavenged and reduced the production of intracellular reactive oxygen species in the LPS stimulated cells. It was also found that the copolymer nanoparticles released HBA which was able to inhibit the production of nitric oxide (NO) by suppressing the expression of inducible nitric oxide synthase (iNOS) in LPS-stimulated cells. The remarkable features of these copolymers are that the copolymer fully degrades into small molecules and one of degradation products is a pharmaceutically active compound. We anticipate that HPOX are highly potent and versatile for the treatment of inflammatory diseases such as allergic asthma.
9:00 PM - MM10.25
Fibrinogen Adsorption on Hydroxyapatite, Carbonate Apatite and Gold Surfaces In Situ Detected by Quartz Crystal Microbalance with Resistance Technique.
Hiroshi Yonekura 1 , Motohiro Tagaya 1 , Tomohiko Yoshioka 1 , Toshiyuki Ikoma 1 , Junzo Tanaka 1
1 Department of Metallurgy and Ceramics Science, Tokyo Institute of Technology, Tokyo Japan
Show AbstractWhen a biomaterial is implanted into the body, blood proteins adsorb on the surface and subsequently cells adhere through the protein adlayer. Thus, the understanding of protein adsorption and conformational changes on the biomaterial surfaces is of great importance to control the biocompatibility such as antithrombotic properties and cell adhesion behaviors. Quartz crystal microbalance with resistance (QCM-R) can measure the changes of resonant frequency and resonant resistance caused with the interactions of proteins and cells on the quartz oscillator during the measurement as weight and viscosity, respectively. The weight of adsorbed substitute is proportional to the decrease in resonant frequency, and viscosity is proportional to the square of resonant resistance. In this study, we fabricated hydroxyapatite (HAp; Ca10(PO4)6(OH)2) and B-type carbonate apatite (CAp; Ca10-xNax(PO4)6-x(CO3)x(OH)2) nanocrystal sensors, and in situ monitored adsorption behavior of fibrinogen (Fgn) on the HAp, CAp and gold (Au) surfaces by the QCM-R technique to clarify the effect of carbonate ions on the interfacial phenomena with the adsorption.The HAp and CAp nanocrystals were synthesized by a wet method, and characterized by X-ray diffraction (XRD), fourier transform infrared spectroscopy (FT-IR), and induced coupled plasma (ICP). The HAp and CAp sensors were fabricated with an electrophoretic deposition method. The surface properties were analyzed by atomic force microscopy (AFM) and FT-IR. Fgn was dissolved into carbonate buffered saline with 30 mM carbonate ions (CBS, pH=8.0). The adsorption behavior of Fgn was in situ monitored by injecting 1 mg/ml of Fgn solution into a flow cell for 3 minutes, and the values of resonant frequency and resonant resistance with the quartz oscillator were recorded for 2 hours.The resonant frequency clearly decreased due to the adsorption of Fgn, and the changes showed the different behaviors depending on the surfaces. The adsorption equilibrium in the frequency occurred within 20 minutes on Au surface, and the resonant frequency on HAp and CAp decreased slower than that on the Au. This indicates that Fgn adsorbed fastest on the Au surface. On the other hand, the resistance changes were significantly larger on the CAp surface than the other surfaces. This indicates that Fgn perpendicularly and viscously adsorbed on the CAp surface. It is known that the Fgn molecule consists of the charged domains (three negatively charged domains and two positively charged domains). Thus, these results are attributed to the difference of binding force between Fgn and the surfaces; Fgn would adsorb on the Au surface with hydrophobic interactions and on HAp and CAp surface with electrostatic interactions. We concluded that the manners of the adsorbed Fgn depend on the three surface properties.
9:00 PM - MM10.26
Dual Roles of Hyaluronic Acid for Drug Delivery Multilayer Platforms.
Saibom Park 1 , Wan-Geun La 2 , Jinhwa Seo 1 , Suk Ho Bang 2 , Byung-Soo Kim 2 , Kookheon Char 1
1 The National Creative Research Initiative Center for Intelligent Hybrids, School of Chemical and Biological Engineering, Seoul National University, Seoul Korea (the Republic of), 2 School of Chemical and Biological Engineering, Seoul National University, Seoul Korea (the Republic of)
Show AbstractFunctional drug delivery platforms that can effectively incorporate and release bioactive nanomaterials such as drugs, growth factors and nanocarriers (NC) have received much attention owing to their useful biomedical implications. Among various functional biodegradable platforms, hydrogel matrices and layer-by-layer (LbL) assembled multilayer films could be powerful candidates, but they have several drawbacks such as rapid washout by biofluids and the requirement of additional modification to incorporate bioactive nanomaterials within the multilayer films. In the present study, we demonstrate biodegradable hyaluronic acid (HA) multilayer films capturing NCs for drug delivery platforms. The electrostatic interactions between linear polyethylene imine (LPEI) and HA provide a driving force for the LbL assembly of multilayers. The physically crosslinked gel-like structure of HA originates from (intra and inter) hydrogen bonding and chain entanglements among HA chains capable of easily capturing NCs within HA. By taking advantages of these capturing capabilities of HA, we were able to locate the specific conditions for HA performing dual roles (i.e., LbL multilayer formation as well as NC capturing) mentioned above. We also note that the amount of NCs captured within the multilayer films is controlled by altering the bilayer number of multilayers as well as chain length and number density of HA chains. We verified the excellent biocompatibility of HA multilayer films by culturing human dermal fibroblast cells as well as the gradual film degradation in physiological condition (pH 7.4) for about 30 days. To confirm that the HA multilayer platform can be applied to stent coatings to regulate restenosis after implantation, we prepared anti-proliferative HA multilayer films capturing paclitaxel-loaded block copolymer micelles (PTXHA platform). The released paclitaxel activity for a desired period successfully prevents the proliferation of human aortic smooth muscle cells that mainly causes restenosis. The results demonstrated in the present study represent the facile incorporation and controlled release of various active drugs, leading to useful biomedical platforms for implant device coatings in orthodontics, orthopedics and cardiovascular application as well as for cancer therapy through the paclitaxel delivery.
9:00 PM - MM10.27
In Vitro and In Vivo Confocal Microscopy for Target Specific Delivery of Hyaluronic Acid Derivatives as a Drug Carrier.
Ki Su Kim 1 , Seonghoon Kim 2 , Eunji Gho 1 , Yi Rang Kim 2 , Hyemin Kim 1 , Seok Hyun Yun 2 3 , Sei Kwang Hahn 1
1 Department of Materials Science and Engineering, POSTECH, Pohang, Kyungbuk, Korea (the Republic of), 2 Graduate School of Nanoscience and Technology, KAIST, Daejon Korea (the Republic of), 3 Wellman Center for Photomedicine, Harvard Medical School, Boston, Massachusetts, United States
Show AbstractHyaluronic acid (HA), which is a biocompatible, biodegradable, and linear polysaccharide in the body, has been widely used for various medical applications. In this work, real-time bioimaging for target specific delivery of HA derivatives was carried out using quantum dots (QDot). In vitro confocal microscopy of HA-QDot conjugates visualized the target specific delivery of HA derivatives to B16F1 cells with HA receptors by HA receptor mediated endocytosis. Furthermore, in vivo real-time confocal microscopy of HA-QDot conjugates successfully visualized the target specific delivery and distribution of HA-QDot conjugates to the fluorescence-labeled blood vessels of liver tissues. Encouraged by the results, we carried out a real-time bioimaging of doxorubicin (DOX) loaded HA - anti-Flt1 peptide conjugate micelles after tail vein injection. In vivo real-time confocal microscopy revealed that HA - anti-Flt1 peptide/DOX micelles were target-specifically delivered to the liver and accumulated in the hepatocytes. The in vivo real time confocal microscopy would be successfully exploited as a new bioimaging tool of HA derivatives for various drug delivery applications.
9:00 PM - MM10.3
Cationic Biodegradable Poly(Amino Oxalate) Particles for Enhanced Intracellular Drug Delivery.
Hyungmin Kim 1 , Jeongil Kwon 1 , Kyeong-Hye Guk 1 , Seunggyu Park 1 , Gilson Khang 2 , Dongwon Lee 1 2
1 Department of BIN Fusion Technology, Chonbuk National University, Jeonju, Chonbuk, Korea (the Republic of), 2 Polymer/Nano Science and Technology, Chonbuk National University, Jeonju, Chonbuk, Korea (the Republic of)
Show AbstractDrug carriers based on cationic biodegradable polymers have attracted much attention because they can facilitate cell uptake and enhance the therapeutic efficacy of their macromolecular payload by rapid endosomal escape via a proton sponge effect. Drug delivery systems for the treatment of many acute inflammatory diseases require fast release of drugs to the diseased site within several hours and non-inflammatory degradation products. In this study, we report new protein delivery systems based on cationic biodegradable poly(amino oxalate) (PAOX) that enhance cellular uptake and are capable of disrupting endosomes, leading to improved cytosolic drug delivery. PAOX synthesized from a one-step reaction of oxalyl chloride, cyclohexanedimethanol and piperazinediethanol had peroxalate ester linkages and tertiary amino group in its backbone. PAOX showed a pH-dependent hydrolytic degradation, with a half-life of 36 h at pH 7.4 and 14 h at pH 5.5 under physiological conditions. PAOX was hydrophobic enough to be formulated into nano- or microparticles by an emulsion/solvent evaporation method. Empty PAOX nanoparticles were round spheres with an average diameter of 450 nm with acceptable yields, >70 %. Protein-loaded PAOX nanoparticles had a 1.5 μm in diameter. Cytotoxicity test based on MTT assay revealed that PAOX had excellent cytotoxicity profiles, comparable to PLGA. An membrane impermeable fluorescent molecule calcein assay revealed that PAOX particles disrupted endosomes via “proton sponge” effects. Catalase-loaded PAOX microparticles significantly inhibited hydrogen peroxide generation in Phorbol-12-myristate-13-acetate (PMA)-stimulated macrophages, in a dose-dependent manner. In summary, the presence of tertiary amine groups in the PAOX backbone induced hydrolytic nature and cationic nature, which results in fast drug release profile and the “proton sponge”effect. Based on excellent biocompatibility and physicochemical properties, we anticipate that PAOX is a promising cytosolic protein delivery system and useful for the treatment of acute inflammatory diseases.
9:00 PM - MM10.4
Chemical Stabilization of Au@Ag Core-Shell Nanoparticles via Electron Transfer.
Cheshta Shankar 1 , Anh Dao 1 , Prerna Singh 1 , Derrick Mott 1 , Shinya Maenosono 1
1 Material Science, JAIST, Nomi , Ishikawa, Japan
Show AbstractMetal nanoparticles (NPs) have received much attention in the past several decades because of their intriguing applications in optics, electronics and chemical/biological sensing. The most common metals used in this field are silver and gold. Silver possesses excellent optical properties, while gold is bio-compatible, resists oxidation, and has a beneficial and unique sulfur reactivity. As a result, many researchers have attempted to couple silver and gold in a single functional core@shell particle. Ag@Au NPs have received much attention because of the beneficial optical properties of silver (high extinction coefficient, well defined surface Plasmon resonance band, etc), and the bio-molecular reactivity and bio-compatibility properties of gold. However, because of the galvanic replacement reaction, it is virtually impossible to synthesize these probes with uniform size, shape and composition, which is required to manipulate their optical properties for practical sensing/diagnostics applications. Another strategy however, is to modify the electronic properties of the NP probe towards resisting oxidation. It has been predicted that an electron transfer phenomena exists between gold and silver in the inverted Au@Ag structure. Such a phenomenon could enhance the Ag stability towards resisting oxidation and is also expected to improve the chemical stability of Au@Ag NPs in the presence of various electrolytes (especially Cl- containing salts). In our own research we synthesized Au@Ag NPs by the citrate reduction method with an Au core size of 13 nm and various Ag shell thicknesses ranging from 2 to 8 nm. The different NPs were used as probes to study the relative stability in various electrolytes (i.e. NaCl, CaCl2, etc.) which was then compared with that for pure Ag and Au NPs. The results are discussed in terms of the propensity for the NPs to be oxidized or for the particles to undergo aggregation and precipitation. The results of this study are expected to lead to a greater understanding for how to control the chemical stability as well as the optical properties of this class of bio-molecular probe.
9:00 PM - MM10.5
Corrosion Resistance of Amorphous Alumina Deposited Nitinol Stent by Atomic Layer Deposition.
Kyoung-Seok Lee 1 , Young-Keun Jeong 1 , Se-Hun Kwon 1
1 National Core Research Center for Hybrid Materials Solution, Pusan Natioal University, Busan Korea (the Republic of)
Show AbstractNitinol alloy has good corrosion resistance and biocompatibility. However, the corrosion resistance of nitinol is highly dependent on the surface condition. Materials with as-drawn and heat-treated surfaces are more susceptible to pitting corrosion due to the presence of heavy oxide and processing contamination. In this study, we deposited alumina on the nitinol surface to improve the anti corrosion of nitinol stent, because it has excellent corrosion resistance.Alumina was deposited by atomic layer deposition (ALD) method. Tri-Methyl Aluminum(TMA) was used as the Al precursor. We prepared control stents and alumina deposited stents of 10, 20 and 40nm thickness. The coated alumina layer on nitinol stents has an amorphous structure because of low process temperature. The breakdown potential for corrosion resistance of all samples was measured by ASTM F2129 method. The breakdown potential of control stent is 200mV, and optical microscope investigation of the stents after corrosion testing revealed that in most cases, localized corrosion (pitting) did occur on the damaged surface area of the stent. With increasing the thickness of alumina layer, the breakdown potential is increased, and the pitting is decreased. The breakdown potential of 450mV can be achieved at the nitinol stent of 40nm alumina.
9:00 PM - MM10.6
Synthesis and Characteristics of Multifunctional SERS Tags Based on Au-Ag Bimetallic Nanoparticles.
Si Yue Li 1 , Min Wang 1
1 Department of Mechanical Engineering, The University of Hong Kong, Hong Kong Hong Kong
Show AbstractCurrently, there is a great interest in developing metallic nanoparticle (NP)-based nanodevices for biomedical applications. Among metallic NPs, the bimetallic Au-Ag NP is most attractive due to its high absorption capability and plasmon resonances in the UV-vis-NIR range, which makes it uniquely suitable for many applications in the biomedical field. In recent years, NPs exhibiting surface enhanced Raman scattering (SERS) have emerged as a new class of tags for biological detection. SERS tags offer two major advantages: high sensitivity and the multiplex detection capability owing to their molecular narrow band spectra. For core-shell structured, flower-shaped Au-Ag NPs, an intensity enhancement factor of 104–106 may be achieved as a result of the signal increase in gaps between metallic nanoparticles and near sharp tips of the flower-like structure, which is sufficient for obtaining Raman signals large enough to enable single molecule detection. In the current investigation, flower-shaped Au-Ag NPs (~90 nm in diameter), which consisted of an Au core and a highly branched Ag shell, were synthesized for the development of multifunctional SERS tags. The shape and thickness of the Ag shell, which significantly affect the optical property of Au-Ag NPs, could be altered by changing the amount of Ag precursor in solutions during Au-Ag NP synthesis. Time-course measurements by UV-vis spectroscopy, HRTEM and STEM-EDX were made to follow the reaction progress and the evolution of the flower-like shape of Au-Ag NPs. Compared to Au NPs or Ag NPs, bimetallic Au-Ag NPs displayed higher SERS. For developing multifunctional SERS tags, a Raman reporter Rhodamine B (RhB) was adsorbed onto Au-Ag NPs first. A folic acid-chitosan polymer conjugate shell was then formed on RhB@Au-Ag NPs, making the multifunctional SERS tag. The folic acid-chitosan conjugate coated RhB@Au-Ag NPs were stable in aqueous solutions over a broad range of pH and ionic strength values. The receptor for folic acid constitutes a useful target for tumor specific delivery, which facilitates easy internalization of the nanodevice through cell membrane. Therefore, the nanodevice created will be able to target tumor biomarkers such as folate receptors on cancer cells through the folic acid on the device surface. The folic acid-chitosan polymer shell will also allow further bioconjugation for achieving other functions for the nanodevice.
9:00 PM - MM10.7
Pulse Laser Deposition of ZnO Thin Films: Growth, Characterization, and Antibacterial Performance.
Mohammad Reza Bayati 1 , Roger J. Narayan 2 1 , Jagdish (Jay) Narayan 1
1 Materials Science and Engineering, North Carolina State University, Raleigh, North Carolina, United States, 2 Biomedical Engineering, North Carolina State University, Raleigh, North Carolina, United States
Show AbstractZnO thin films were grown onto sapphire (0001) substrate by pulse laser deposition method at substrate temperature of 150 oC under different oxygen pressures ranging from 10-3 to 10+1 Torr. Based on the X-ray diffraction results, the layers had a highly textured crystallographic structure with a (002) orientation where intensity of the ZnO (002) peak increased and, then, decreased with the oxygen pressure. The lowest FWHM and maximum intensity were obtained under the pressure of 10-1 Torr. Changes in intensity and FWHM of the XRD peaks were interpreted according to the defect structure in the film crystalline lattice and kinetic energy of the ablated species from the target surface. Based on the XPS results, concentration of the oxygen vacancies decreased with the ambient pressure. Optical properties of the layers were also studies employing a UV-Vis spectrophotometer. The layers fabricated under intermediate oxygen pressures, i.e. 10-1 and 100 Torr, exhibited a sharper transmittance edge due to their lower defects concentration. Finally, the antibacterial efficiency of the layers was studied under UV-irradiation. The layer grown under the pressure of 10-1 Torr exhibited the best antibacterial performance.
9:00 PM - MM10.8
Effect of Atomic-Scale Topography and Ligand Density on Nanoparticle-Adsorbed Protein Structure and Function.
Jennifer Gagner 1 2 , Xi Qian 1 2 , Jonathan Dordick 1 2 3 , Richard Siegel 1 2
1 Materials Science & Engineering, Rensselaer Polytechnic instiute, Troy, New York, United States, 2 Rensselaer Nanotechnology Center, Rensselaer Polytechnic Institute, Troy, New York, United States, 3 Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, New York, United States
Show AbstractMany applications of nanobiomaterials rely on or are enhanced by specific, protein-mediated interactions with biological systems. These interactions can be engineered by chemically modifying the surface of the material to affect protein adsorption, or by altering the topography of the nanoscale surface. The attachment or adsorption of proteins onto materials can greatly affect the structure and subsequent function of those proteins, giving rise to unpredictable and potentially undesirable effects. Thus, it is essential to develop a detailed understanding of how nanostructured surface characteristics, such as atomic-scale topography, surface energy, and chemical structure may affect protein adsorption, structure, function, and stability. Our recent work on gold nanospheres and nanorods has clearly elucidated the effect of nanoparticle morphology in protein adsorption, finding that morphology does determine the extent and surface density of adsorbed proteins. In the current study, a model system of precisely engineered nanoparticles is used to determine the role of crystal structure, surface energy, and ligand chemistry on the structural and functional properties of adsorbed proteins. Wet chemical methods are used to synthesize gold nanocubes with {100} facets and gold nanooctahedra with {111} facets. Nanoparticle populations are thoroughly characterized through electron microscopy (TEM, SEM), X-ray and electron diffraction, X-ray photoelectron spectroscopy, and inductively coupled plasma mass spectroscopy. The proteins lysozyme, α-chymotrypsin, horseradish peroxidase, and cytochrome c are then adsorbed onto the nanoparticle surfaces. Perturbations in the protein structure are monitored globally and locally via circular dichroism and surface enhanced Raman spectroscopy, isothermal titration calorimetry, and enzyme assays. Although many current studies have focused primarily on exploiting nanostructured material properties for biomedical applications, insufficient identification and understanding of key variables involving the protein-nanomaterial interface hinder the development and subsequent full potential of nanobiomaterials. Fundamental understanding of how these factors affect protein structure and function will assist in the strategic engineering of protein-nanomaterial conjugates for a variety of important biomedical applications.This work was supported by the US National Science Foundation under Grant No. DMR-0642573.
9:00 PM - MM10.9
Development of Bisphosphonate-Calcium Phosphate Composites and Drug Release Characteristic.
Hidekuni Kameda 1 , Tomohiko Yoshioka 1 , Toshiyuki Ikoma 1 , Junzo Tanaka 1
1 Department of Metallurgy and Ceramics Science, Tokyo Institute of Technology, Tokyo Japan
Show AbstractRecently, the number of the patients who suffer from osteoporosis has increased in step with the aging of the population. Bisphosphonate (Bp) has been used to treat osteoporosis. However, oral administration of Bp often causes severe side effects such as osteonecrosis of the jaw. As a solution for this problem, the treatment method that uses drug carriers is attracting a great deal of attention. Drug delivery system (DDS) has been widely investigated from the points of view of clinical and material-engineering to reduce side effects and to improve efficacy of drugs. The ideal administration of a drug is to deliver a required amount of the drug to a necessary organ for an effective term. Calcium phosphate (CP) is a biocompatible carrier desirable for drugs such as Bp. When the carrier including Bp is locally administrated into an osteoporosis region, it is expected that the resorption of bone induces the release of Bp from the carrier implanted. The purpose of this study is to develop composites of Bp and CP as a novel drug delivery carrier.In the experiments, sodium etidronate was used as Bp. The composites of Bp and CP were synthesized by titrating calcium acetate solution (0.04 M, 250 ml) into phosphate buffer solution (0.04 M, 200 ml, pH6.7) containing 300 mg of Bp. After stirring for 3 h, the precipitations were filtered and dried at 310 K. The releasing property of Bp from the composites was conducted in vitro, i.e. in both acetate buffer solution (pH5.5) and phosphate buffered saline (PBS, pH7.2) at 310 K. The acetate buffer solution is considered to reproduce the similar condition of osteoclastic bone resorption. The amount of released Bp was determined from absorption intensity at 233 nm of Bp-FeSO4 complex using a UV-visible spectrometer.XRD and FT-IR measurements exhibited that the composites obtained was an amorphous calcium phosphate including Bp. The amount of Bp doped in the composite was 366 μg / mg. TG-DTA measurements of Bp (Bp or calcium-Bp) and the composite indicated an exothermic peak of carbon combustion from Bp, of which temperatures were shifted to higher temperature for the composite. From these results, Bp was successfully doped into the CP. Bp in the composites was gradually released into the PBS, while Bp was rapidly released into the acetate buffer solution accompanying with the dissolution of CP. This result suggests that the composite precipitated has potential for a drug-carrier releasing Bp in response to the condition of osteoclastic bone resorption.
Symposium Organizers
Roger Narayan University of North Carolina and
North Carolina State University
Seeram Ramakrishna National University of Singapore
Vipul Dave Cordis Corporation, a Johnson & Johnson Company
Donglu Shi University of Cincinnati
Sungho Jin University of California-San Diego
MM11
Session Chairs
Ahmet Ozenbas
Jacqueline Sturgeon
Friday AM, December 02, 2011
Room 206 (Hynes)
9:00 AM - MM11.1
Multi-Scale Engineering for Adult Human Stem Cells Growth and Differentiation.
Amelie Beduer 1 2 3 , Laurence Vaysse 4 5 , Isabelle Loubinoux 4 5 , Emmanuel Flahaut 6 2 , Vieu Christophe 1 2 3
1 , CNRS-LAAS, Toulouse France, 2 , Université de Toulouse, UPS, INSA, INP, ISAE, LAAS, Toulouse France, 3 , ITAV-Centre Pierre Potier, Toulouse France, 4 , INSERM-UMR825, Toulouse France, 5 , Université de Toulouse, UPS, UMR 825, CHU Purpan, Toulouse France, 6 , Université de Toulouse, UPS, INP, Institut Carnot CIRIMAT, Toulouse France
Show AbstractThird leading cause of mortality, stroke is the first cause of handicap in adult. Destruction of corticospinal tract has been identified as a crucial issue, impeding a good recovery. To really reconstruct a corticospinal tract in the needed direction, from the damaged cortex to a subcortical level in junction with the original fibers pathway, we propose to design an implantable scaffold. This engineered material hosts neural cells and exhibits micrometric and nanometric features capable to induce differenciation and neurite growth in a deterministic direction. Several extracellular signals acting at different length scales (micro and nano) are combined in this system: topographical micrometric grooves inducing a precise alignment of the neurites together with double wall carbon nanotubes (DWCNTs) developing a nanoscale surface roughness acting as a sponge with respect to nutriments and proteins of the culture medium. Moreover, our CCVD synthesized DWCNTS exhibit massively a metallic behaviour which will allow electrical stimulation of the regenerated track. The work presented here synthesizes the results we have obtained in-vitro for characterizing and optimizing the effects of the engineered features on neural cell behaviour but will not focus on the in-vivo effects investigated in rats.Adult human neural stem cells were cultured on a microgrooved polymer, the PolyDiMethylSiloxane (PDMS), which is inert and biocompatible. This material was conventionally microstructured using a simple molding process against a silicon master, and used after specific coatings for the cell culture. A systematic study has been implemented for optimizing the width and depth of the grooves in order to obtain a maximum differentiation rate of stem cells in neurons and a precise alignment of the produced neurites along the groove axis. We demonstrate further that the chemically coated PDMS microchannels are adapted to the long term human neural stem cells culture. To investigate the interactions between neural cells and nanoscale features, we created DWCNTs layers. The realization of DWCNTs micropatterns lead us to show that neural cells preferentially grow and differentiate on DWCNTs areas. In order to elucidate how carbon nanotubes influence cell behaviour, we studied more precisely the interactions of culture medium elements with CNTs layers thanks to Quartz crystal Microbalance (QCM-D) experiments. We clearly observe that CNTs patterns act as a sponge for culture medium nutriments and differentiation agents and constitute a kind of oasis for cells. The benefits of our DWCNTs coated microstructured polymer devices are very promising for improving performances of brain implantable scaffolds and brain-electrodes.
9:15 AM - MM11.2
Microfluidic Fabrication of Yeast Cell Assemblies.
Ya-Wen Chang 1 , Peng He 1 , Samantha Marquez 2 , Zhengdong Cheng 1 , Manuel Marquez 3
1 Artie Mcferrin Department of Chemical Engineering, Texas A&M University, College Station, Texas, United States, 2 , Maggie L. Walker Governor's School for Government and International Studies, Richmond, Virginia, United States, 3 , YNano LLC, Midlothian, Virginia, United States
Show AbstractWe present microfluidic approaches to fabricate Yeastosome® (Yeast-Celloidosome®) based on interfacial self assembly. As the surface charge of the building blocks can be readily modified by layer-by-layer polyelectrolyte deposition, we guide the cells’ organization via electrostatic interactions. The central strategy to this structure-building is the employment of droplet/bubble formation microfluidic devices to produce precise liquid-liquid/ liquid-gas templates for assembly. We demonstrate that by engineering the electrostatic driving forces between the interfaces, complex core-shelled Yeastosome® structures can be obtained. The combination of microfluidic fabrication with cell self-assembly enables versatile platform for designing synthetic hierarchy bio-structures.
9:30 AM - MM11.3
Microscale Cell Printing in Photocrosslinkable Three Dimensional Matrix Materials.
William Hynes 1 , Nathaniel Doty 2 , Thomas Zarembinski 2 , Nathaniel Cady 1
1 College of Nanoscale Science & Engineering, University at Albany, Albany, New York, United States, 2 A Division of Orthocyte Corp., Glycosan BioSystems, Salt Lake City, Utah, United States
Show AbstractPatterning of living cells on solid surfaces has applications for cell-based screening assays, tissue engineering, cell signaling studies, as well as for the development of hybrid nanodevices and biosensors. We have previously demonstrated micrometer scale, live-cell printing of both bacterial and mammalian cells using this method. A challenge for this approach has been immobilization and retention of cells on growth substrates. To overcome this challenge, biocompatible hydrogel matrices based on crosslinking thiol-modified hyaluronate (HA) and thiol-modified gelatin with polyethylene glycol diacrylate (PEGDA) have been adopted as a 3D matrix material for cell printing. Using this matrix, NIH 3T3 fibroblasts, mouse embryonic stem cells, and multiple bacterial species were successfully printed and maintained on solid surfaces. Cell viability and proliferation were observed for as long as four days post-printing and cell signaling/response could be directly observed with bacterial quorum sensing sender/receiver strains. Although this approach was both versatile and resulted in high cell viability/ proliferation, it was limited by slow (10-20 min) matrix gelation times, which limited its utility for precise spatial and temporal patterning experiments. Improved gelation time and printing precision was obtained by adopting a novel crosslinker composed of a 4-arm polyethylene glycol functionalized with norbornene moieties (PEG norbornene) as a replacement for PEGDA in the thiolated HA platform described above. These components in combination with 0.05% Irgacure 2959, 1% PEG norbornene and UV light (365 nm) undergo thiol-norbornene (thiol-ene) photopolymerization in as little as 15 sec. Mammalian and bacterial cell viability, proliferation and signaling were evaluated for this improved matrix material, showing little deviation from the non-UV cured matrix. The development of this thiol-ene polymerization system in conjunction with previously developed thiol-based hydrogel systems provided substantially more control over gelation and enabled improved accuracy and precision for spatial patterning of cells, within a 3D matrix material.
9:45 AM - MM11.4
Spatially Controllable Deposition of Electrospray Micro/Nanoparticles.
Xu Zhang 1 , Yi Zhao 1
1 Biomedical Engineering Department, Ohio State University, Columbus, Ohio, United States
Show AbstractElectrospray has been widely used in micro/nanotechnology for depositing microparticles. However, conventional approaches exhibit poor control of particle distribution on the collecting surface. This work introduces a programmable patterning method of electrospray microparticles using micropatterned collecting chips. By manipulating the local electric field, good spatial control of microparticles is demonstrated.Polycaprolactone(PCL) solutions are prepared by mixing 10wt% PCL with acetone. Electrospray is performed with a voltage bias of 20kV DC, a spray distance of15cm, and the flow rate of 0.5ml/hr. Linear microelectrodes array with the electrode width of 200um and the interelectrode distance of 1000um is used as the collector, which are fabricated by standard photolithography.Experiments are designed following two protocols. In protocol 1, all electrodes are connected to the ground. The results show that after 30 seconds spray the density of particles depositing on the electrodes area (12.2±0.77 per 1000 um2) is nearly five times to those on the interelectrode area (2.6±0.63 per 1000 um2).The average radius of particles on electrode area is 1.4(±0.10) um, while that of particles on interelectrode area is 1.8(±0.05) um. The heterogeneity in particle-size distribution may be attributed to the different surface-to-volume ratios: small particles have relatively large surface-to-volume ratios, thus are more susceptible to local electric field. In protocol 2, the electrodes fingers are divided into two groups. One group is grounded while the other is floating. The floating fingers and the grounded fingers arranges alternatively. The number of particles depositing on the electrodes area (12.7±0.60 per 1000 um2) is more than six times to those on the interelectrode area (1.9±0.70 per 1000 um2). This result is in good agreement with our theoretical analysis that the floating electrodes play a critical role for enhancingthe patterning contrast. Similar to the result in protocol 1, average radius of particles on electrode area (1.9±0.07um) is smaller than that of particles on interelectrode area (2.7±0.18um).This method provides a simple yet highly reliable approach for creating patterned polymer micro/nanoparticles. Combined with encapsulation technique, this unique method promises potential applications in cell patterning, cell sorting as well as other important applications in functional cell/tissue engineering.
10:00 AM - MM11.5
Alginate and Poly(Ethylene Glycol) Copolymer Microspheres for the Controlled Delivery of Genetic Material.
Rachael Oldinski 1 , Kristy Katzenmeyer 1 , James Bryers 1
1 Bioengineering, University of Washington, Seattle, Washington, United States
Show AbstractAlginate (AA) particles have been investigated to deliver cells and drugs in vivo; however, their application is limited due to their large diameters and negative charge. The following study investigated the fabrication of AA and poly(ethylene glycol) copolymer microspheres for the delivery of genetic vaccines. The goal of the study was to fabricate microspheres that were uniform in size, encapsulated a high amount of drug and offered protection against degradation of the genetic material. Microsphere morphology and diameter, vaccine release rates, and macrophage transfection were examined. Alginate (170 kDa and 240 kDa) was modified with methoxy-terminated PEG amine (500 Da) using carbodiimide and N-hydroxysuccinimide chemistry; the copolymer was characterized by 1H-NMR. FITC-terminated PEG was used for the phagocytosis experiments. Plasmid DNA (gWIZ-GFP) was complexed with poly(ethyleneimine) to form a polyplex with an N:P ratio of 5. Polyplex-encapsulated AA-co-PEG microspheres were fabricated using a water-oil emulsion reaction and calcium crosslinking. Microsphere morphology, diameter and surface charge were characterized by scanning electron microscopy (SEM) and dynamic light scattering (DLS). The encapsulation efficiency and release rate of pDNA from microspheres under physiological conditions was quantified by UV spectrometry. Phagocytosis, cytotoxicity and transfection assays were performed using a macrophage cell line under standard culture conditions. Increasing AA molecular weight, increasing AA concentration, and increasing the degree of PEG conjugation increased microsphere diameter; microspheres measured 500 nm – 5 µm in diameter. AA-co-PEG microspheres were uniform in size (per batch) and spherical in shape. Microspheres consisting of high molecular weight AA formed large aggregates in solution. Microsphere cytotoxicity was dependent on concentration molecular weight of the AA. PEG copolymerization increased cytotoxic effects at low concentrations. 1 µm in diameter were internalized by macrophages after 24 h of culture. Increasing the degree of PEG conjugation increased encapsulation efficiency. Increasing AA molecular weight prolonged DNA release, and decreasing the polymer concentration increased release rate. The pDNA remained active after microsphere fabrication and macrophages were successfully transfected after 48 hours of culture with AA-co-PEG microspheres. Trends appeared which demonstrated that increasing AA molecular weight and increasing the degree of PEG conjugation enhanced transfection. The diameter of AA-co-PEG microspheres and release rate of complexed pDNA were altered by varying the molecular weight and ratio of copolymer constituents. The genetic material remains viable after microsphere fabrication. Future experiments will investigate the effect of enteric coatings with cell targeting moieties and the incorporation of AA-co-PEG microspheres into tissue engineering scaffolds for optimizing gene delivery.
10:15 AM - **MM11.6
Formation of Calcium-Deficient Fluoridated Apatite from β-Tricalcium Phosphate at Physiologic Temperature.
Jacqueline Sturgeon 1 , Paul Brown 2
1 , RJ Lee Group, Inc., Monroeville, Pennsylvania, United States, 2 , Penn State University, University Park, Pennsylvania, United States
Show AbstractHuman tooth enamel is primarily comprised of a fluoride substituted apatite with a calcium to phosphate ratio of less than 1.67, the ratio of a fully stoichiometric apatite. Thus, establishing the formation of a calcium-deficient fluoridated apatite (CDFAp) is of importance for understanding the behavior of enamel and potentially for caries remediation. This study investigated the synthesis of CDFAp by hydrolysis of β-tricalcium phosphate (β-TCP) in NH4F solutions with varying concentrations at physiologic temperature; reaction in water was used as a control. The morphology of the apatite formed and conversion rate are strongly influenced by the amount of fluoride available. Phase evolution was assessed using x-ray diffraction, and lattice parameters were also calculated using XRD. The solution chemistry was followed for up to 8 weeks of reaction; formation of CDFAp with Ca/P ratios typically near 1.6 was confirmed. FTIR spectra indicate both carbonate and fluoride incorporation. Morphology was examined using scanning electron microscopy; at high fluoride concentrations, the apatite crystals formed are approximately 0.9μm in length and 0.2μm in diameter. In comparison, apatite crystals formed from β-TCP reacted in water are longer and thinner. The formation of FAp from β-TCP is theorized to occur by rapid formation of the FAp phase followed by slow hydrolysis of the remaining β-TCP.
11:00 AM - **MM11.7
Lithographically Patterned Porous Carbon Electrodes.
Ronen Polsky 1 , Xiaoyin Xiao 1 , Cody Washburn 1 , David Wheeler 1 , Susan Brozik 1 , Thayne Edwards 1 , Sirilak Sattayasamitsathit 2 , Aiofe O'Mahoney 2 , Joseph Wang 2 , D. Bruce Burckel 1
1 Biosensors & Nanomaterials, Sandia National Laboratories, Albuquerque, New Mexico, United States, 2 Department of Nanoengineering, University of California, San Diego, La Jolla, California, United States
Show AbstractPyrolyzed Photoresist Films (PPF) have electrochemical properties similar to glassy carbon electrodes with the unique feature that they can be lithographically defined to create microstructures and microfeatures. Porous carbon electrodes were fabricated by interferometric lithography (IL) to generate 3-D periodic structures in PPF that contain five patterned layers with microporous hexagonal lattices (~ 800 nm in diameter). [1] Because IL is a maskless approach porous carbon structures are able to be produced with defect-free 3-D lattices and sub-wavelength periodicity uniformly over large volumetric areas in excess of 2 cm a side. Despite a high degree of interconnectivity, the relatively large pore sizes preserve hemispherical diffusion inside the structures which exhibit diffusion profiles similar to microelectrodes. [2] We demonstrate that these porous carbon structures can be used as a highly adaptable electrode material with increased mass transport properties for the deposition of metal nanoparticles and conducting polymers with applications in such areas as fuel cells, ultracapacitors, and sensors. [1] a) D. B. Burckel, C. M. Washburn, A. K. Raub, S. R. J. Brueck, D. R. Wheeler, S. M. Brozik, and R. Polsky Small 2009 5, 2792-2796. [2] X. Xiao, M.E. Roberts, D.R. Wheeler, C.M. Washburn, T.L. Edwards, S.M. Brozik, G.A. Montaño, B.C. Bunker, D.B. Burckel, R. Polsky, ACS Appl. Mat. and Inter., 2010 2, 3179-3184
11:30 AM - MM11.8
Smart Nanomedicines for the Treatment of Liver Diseases.
Sei Kwang Hahn 1 2 , Eun Ju Oh 1 , Kitae Park 2 , Ki Su Kim 1 , Jeong-A Yang 1
1 Department of Materials Science and Engineering, POSTECH, Pohang, Kyungbuk, Korea (the Republic of), 2 School of Interdisciplinary Bioscience and Bioengineering, POSTECH, Pohang Korea (the Republic of)
Show AbstractNanomedicine is the term for the use of nanotechnology to the medicine. In this work, we developed smart nanomedicines using hyaluronic acid (HA) derivatives for the treatment of liver diseases. HA is a biocompatible, biodegradable, non-toxic, non-immunogenic, and negatively charged polysaccharide in the body. In order for drug delivery applications, real-time bioimaging of HA derivatives was carried out in mice using quantum dots (QDots). HA-QDot conjugates with 35 mol% HA modification were mainly accumulated in the liver with HA receptors, while those with 68 mol% HA modification were evenly distributed in the body. Accordingly, slightly modified HA derivatives were exploited for target specific systemic delivery of siRNA and interferon α (IFN α). After tail-vein injection, apolipoprotein B siRNA/(PEI-SS)-g-HA complex resulted in a gene silencing efficiency up to ca. 80% in a dose-dependent manner. The TGF-β siRNA/(PEI-SS)-g-HA complex showed an excellent therapeutic effect on liver cirrhosis. Moreover, HA – IFN α conjugate significantly increased the expression level of OAS 1 essential for innate immune responses to viral infection. Taken together, the novel HA based drug delivery systems were thought to be effectively applied to the treatment of liver diseases with HA receptors.
11:45 AM - MM11.9
Nano-Structured Contoured Surface Coatings for Orthopaedic Implants.
Alexander Slocum 1 2 , Adam Paxson 1 , Kripa Varanasi 1
1 Mechanical Engineering, MIT, Cambridge, Massachusetts, United States, 2 Joan C Edwards School of Medicine, Marshall University, Huntington, West Virginia, United States
Show AbstractThe application of porous coatings to the surfaces of orthopaedic implants can result in drastic improvements in the degree of integration of the implant into the surrounding tissue, and also the subsequent overall success of the procedure. In some implants, for example the current bio-mimetic arrangement of metal-on-polymer joints used in Total Knee Arthroplasty (TKA), loading conditions result in fracture of the soft polymer bearing surface into nm to micron-sized particles. The body's natural immune response to diffusion of these particles throughout the synovial fluid, referred to as "particle disease", results in periprosthetic osteolysis; bone surrounding the implant is resorbed into the body. This, in addition to stress shielding more commonly seen in the stems of Total Hip Arthroplasty devices, can result in significant bone resorption and subsequent catastrophic failure of the implant. In order to counteract these processes, porous oxide coatings fabricated directly into the surface of implants can be modeled as open-cell foams, and their modulus contoured using nano-fabrication techniques to match that of the adjacent trabecular bone. Additionally, the resulting "elastically averaged" implant/bone interface should increase the degree to which osteoblasts integrate into the implant suggesting formation of a more structurally sound joint. Results of nano-indentation tests on porous coatings will be compared to moduli predicted using a theoretical foam modulus, as well as a proposed method of modeling the coating/implant interface.
12:00 PM - **MM11.10
3-Glycidoxypropyltrimethoxysilane Mediated In Situ Generation of Noble Metal Nanoparticles: Biomedical Applications.
P. Pandey 1
1 Department of Applied Chemistry, Banaras Hindu University, Varanasi India
Show AbstractIn-situ generation of noble metal nanoparticle via 3-glycidoxypropyltrimethoxysilane mediated reduction is reported. The method describes synthesis of uniform spherical nanoparticles of gold, silver and palladium having controlled size that can be directly utilized for thin film preparation. In addition, the material exhibits excellent compatibility towards composite preparation. Detailed report on the formation of gold nanoparticles of two different size are reported. These nanoparticles are further allowed to form their nanocomposite with Prussian blue useful for the fabrication of chemically modified electrode useful in biomedical applications. The resulting CME shows dramatic improvement in electrochemistry with gradual enhancement in electrocatalytic efficiency of Prussian blue to hydrogen peroxide sensing. The Prussian blue composite has been used for direct and HRP-mediated sensing of hydrogen peroxide. The results revealed nano-size-dependent amplification of hydrogen peroxide sensing.
12:30 PM - MM11.11
A Novel Intelligent Magnetic Nanobiomatetial and Its Biomedical Applications.
Feng Xu 1 , Chung-an Wu 1 , Venkatakrishnan Rengarajan 1 , Thomas Finley 1 , Hasan Keles 1 , Yuree Sung 1 , Baoqiang Li 1 , Omer Mullick 1 , Umut Gurkan 1 , Utkan Demirci 1
1 Harvard-MIT Health Sciences and Technology, Harvard-MIT Health Sciences and Technology, Cambridge, Massachusetts, United States
Show AbstractThe future of tissue engineering requires development of intelligent biomaterials using nanoparticles. Recently, we have developed a novel nanobiomaterial, where magnetic nanoparticles (MNPs) have been encapsulated within cell-laden hydrogels (M-gels). The M-gels can be used as building blocks for bottom-up tissue engineering to create 3D complex tissue constructs by assembling building blocks via external magnetic fields at high throughput with spatial control over three-dimensional (3D) micro-architecture. We also developed an approach to form three-dimensional (3D) hydrogel arrays by organizing and assembling M-gels using spatially controlled magnetic fields. Permanent magnet arrays with dielectric spacers were used to control the size and the geometry of the hydrogel arrays. We also studied the release of MNPs from these M-gels as the hydrogels undergo degradation. The degradation rate increased with increasing MNP concentration and the corresponding MNP release was linearly correlated with hydrogel degradation results. Cells remained viable and formed microtissues. These results indicated that MNP encapsulating hydrogels can become promising as intelligent biomaterials, with great potential to impact several areas such as tissue engineering and regenerative medicine, drug release.
12:45 PM - MM11.12
Nanomodified ETT: Reduced Bacterial Colonization in a Bench Top Airway Model.
Mary Machado 1 , Keiko Tarquinio 2 , Thomas Webster 1 3
1 School of Engineering, Brown University, Warwick, Rhode Island, United States, 2 Division of Pediatric Critical Care Medicine, Rhode Island Hospital, Providence, Rhode Island, United States, 3 Department of Orthopaedics, Brown University, Providence, Rhode Island, United States
Show AbstractIntroduction: Despite extensive research into prevention and management, ventilator associated pneumonia (VAP) continues to be a severe, costly complication of mechanical ventilation among critically ill patients. Endotracheal tubes (ETTs) present a special concern to clinicians because they are often colonized by oropharyngeal bacteria during long-term mechanical ventilation. Cost effective ETTs that are resistant to bacterial infection would be essential tools in the prevention of VAP. The objective of this study was two fold, first to develop strategies to decrease bacterial adhesion on ETTs using nanotechnology and secondly to develop better methods to assess in vitro bacterial adhesion and biofilm formation on ETTs using a bench top experimental model and computer simulations of air flow.Materials and Methods: Nanoroughened ETT were created by exposing polyvinyl chloride (PVC) ETTs (Sheridan®) to a 0.1% mass solution of Rhizopus arrhizus (Sigma Aldrich) lipase dissolved in a potassium phosphate buffer. Nanomodified ETTs were tested in a custom made bench top model airway. ETT were connected to an Infant Star 950 ventilator with positive end-expiratory pressure (PEEP) of 1 cmH2O and fraction of inspired oxygen (FiO2) of 0.5. Bacterial media, 480 mL of trypticase soy broth media (TSB) inoculated with 103 Staphylococcus aureus (ATCC #25923), was introduced into the system over the duration of the 24 hour test. At the end of each trial, ETT were cut into ten 1.5 cm pieces. These tubes were either stained with crystal violet and analyzed with optical density or processed using a vortex methodology. Results and Discussion: Twenty-four hour studies performed in the dynamic flow chamber showed a marked difference in the biofilm formation along the length of the tube. Areas of tube curvature, were correlated with larger amounts of bacteria. Notably, the values for biofilm density along many areas of the tube were substantially less than those obtained from previous static studies, highlighting the importance of dynamic media analysis. The computational model of the tube showed variations in the wall shear rates at both curves in the tube, which corresponded to experimental areas of high bacterial density. Conclusions: Dynamic studies show lipase etching can create nano-rough surface features on PVC ETTs that suppresses S. aureus growth. Flow conditions within the ETT influenced both the location and concentration of bacterial growth on the ETT. The differences in both bacterial number and optical density recorded along the length of the tube suggest that wall shear stress plays a significant role in bacterial colonization. The results of both static and dynamic models suggest that nanomodified tubes could provide clinicians with an effective and inexpensive tool to combat hospital acquired infections like VAP, and should be studied in greater depth.Acknowledgements: The authors would like to thank the Hermann Foundation and NSF GK-12 for funding.