Roger Narayan University of North Carolina
Suwan Jayasinghe University College London
Sungho Jin University of California-San Diego
William Mullins Office of Naval Research
Donglu Shi University of Cincinnati
VV1: Functional Materials and Devices
Tuesday AM, December 01, 2009
Room 202 (Hynes)
9:00 AM - VV1.1
Improved Culture Conditions for Measuring T-Lymphocyte Responses for Cell Based Cancer Therapy.
Carole Perry 1 , Graham Hickman 1 , Akhilesh Rai 1 , Balwir Matharoo-Ball 1 , Robert Rees 1 Show Abstract
1 School of Science and Technology, Nottingham Trent University, Nottingham United Kingdom
The interactions between biological systems and biomaterials are of great importance to regenerative medicine. Key to this understanding is assessing how cells react when presented with materials of varying physical and chemical properties. ‘Omics’ technologies such as MALDI mass spectrometry are ideal methods to examine the interactions between cell and surface.To this end we have built upon existing methods for the manufacture of bio-mimetic silica film surfaces with novel chemical and physical properties. Our methods have been able to produce silica surfaces under mild chemical conditions on a range of substrates suitable for use in cell culture applications. These surfaces can be fabricated with characteristics such as wetting properties ranging from hydrophobic to hydrophilic or even super-hydrophilic, depending on the methods used.The initial silica surface produced was trialed as a cell culture surface with a melanoma cell line (FM3) on both a hydrophilic silica surface and conventional cell culture polystyrene. After a period of culturing the culture media and lysed cells were examined using current MALDI based proteomic techniques to generate a peptide mass fingerprint characteristic of the cells cultured on both of the surfaces.Through comparison of the proteomic studies we have determined that the cell culturing surface can have a dramatic effect on the cell proteome. The melanoma line cultured on a hydrophilic silica surface showed a radically altered peptide mass fingerprint as compared with the cells cultured on the traditional cell culture polystyrene surface, both in terms of the proteins expressed into the cell culture media and the proteome of the cell itself. Examination of the morphology of the melanoma cells via optical microscopy showed that while the cells cultured on the different surfaces demonstrated similar morphological characteristics they showed important variations in their expressed proteome.Further investigation with different cells, including different cell surface chemistries in relation to culturing materials with different surface properties should provide great insight into the interactions between biological systems and materials destined for biological applications.
9:15 AM - VV1.2
Cell-Based Detection of Synthetic Pathogens Using Cell Impedance Sensing.
Bhavana Mohanraj 1 , Nate Schiele 1 , Anne Hynes 1 , David Corr 1 , Cerasela Dinu 1 , Douglas Chrisey 1 Show Abstract
1 Materials Science and Engineering Department, Rensselaer Polytechnic Institute, Troy, New York, United States
We demonstrate a new approach to electrically sense pathogens using cells as the receptor-sensing element. Electrical Cell-substrate Impedance Sensing (ECIS) was used to monitor the confluent growth of human dermal fibroblasts and their exposure to an anthrax simulant namely Bacillus cereus. ECIS was conducted at frequencies between 4 – 64 kHz and it was found to be an excellent measure of cell growth, micro-motion, and their overall intracellular and intercellular morphological responses when challenged with various agents. When exposed to the digestive enzyme trypsin we observed an instantaneous and unambiguous change in the capacitance, of approximately 67% at 32 kHz almost instantaneously. When exposed to the anthrax simulant Bacillus cereus spores, we observed no response during germination and a very small response when the bacillus cells thrived in the fibroblast growth media. The ECIS response was consistent with a live-dead assay whereby it was found that no cells had died and no significant morphological change was observed. While Bacillus cereus is in the same genetic family as Bacillus anthracis, its pathological lethality on the cellular level for fibroblasts was negligible. Our work shows that the ECIS measurements were an extremely sensitive measure of fibroblast morphological response. In this presentation, we will challenge prototype biosensors with other biological warfare simulant pathogens such as B. Subtilis or B. Atrophaeus (simulant for smallpox) as well as with against chemical warfare agents dimethyl methyl phosphonate (nerve agent – sarin) and 1,5 dichloropentane (blister agent – mustard gas).
9:30 AM - VV1.3
Implantable BioMEMS for Localized Hyperthermia and Cancer Drug Release.
Yusuf Oni 1 2 , Guoguang Fu 1 2 , Christian Theriault 1 , Alex Van Hoek 1 , Rohith Chandrasekhar 3 , Emily Paetzell 1 2 , Wole Soboyejo 1 2 Show Abstract
1 Mechanical and Aerospace Engineering, Princeton University, Princeton, New Jersey, United States, 2 Princeton Institute for the Science and Technology of Materials, Princeton University, Princeton, New Jersey, United States, 3 Electrical Engineering, Cooper Union, New York, New York, United States
This paper presents a novel implantable bio-micro-electro-mechanical system (Bio-MEMS) device for the localized treatment of cancer. The device uses a combination of heating (hyperthermia) and drug release to kill breast cancer cells. Cancer drug release is controlled by the use of modified poly(N-iso-propyl-acrylamide) (PNIPA) hydrogels with hydrophobic/hydrophilic copolymers and interpenetrating network structures. The gels are encapsulated in biocompatible poly-di-methyl-siloxane (PDMS) with micro-fluidic channels that convey the drug (paxlitaxel) to cancer cells/tissue. The thermo-sensitive properties (swelling) and fluid/drug release characteristics of the gels are elucidated along with the effects of localized heating with micro-wires. A synergistic killing of breast cancer cells is shown to occur as a result of the combined effects of localized cancer drug release and hyperthermia.
9:45 AM - VV1.4
Micro and Nanopatterning Tools to Produce Biomimetic Chips Based on Molecularly Imprinted Polymers.
Cedric Ayela 1 , Helene Lalo 2 , Samuel Guillon 2 , Thierry Leichle 4 , Fanny Vandevelde 3 , Ana Valvanuz Linares 3 , Liviu Nicu 2 , Karsten Haupt 3 Show Abstract
1 , Laboratoire de l'Intégration du Matériau au Système UMR 5218; University of Bordeaux, Talence France, 2 , LAAS-CNRS; University of Toulouse; 7, avenue du Colonel Roche F-31077, toulouse France, 4 , Institute of Physics, Academia Sinica, Taipei 115, Taipei Taiwan, 3 , Univeristé de Technologie de Compiègne, CNRS UMR 6022, Compiègne France
Micro and nanobiochips are of interest in biomedical applications like diagnostic, molecular screening and drug discovery. Recent advances in this field allow introducing technologies to create highly sensitive patterns. Classically, biochips are arrays of natural biomolecules locally immobilized on a surface. However, short life-time and poor stability of natural molecules when used out of their native conditions promotes introduction of alternative sensitive layers, particularly biomimetic polymers. Molecularly imprinted polymers (MIPs) represent a novel area of polymers capable of molecular recognition with the same affinity and selectivity as their natural counterparts. Their synthetic composition offers enhanced long-term stability compared to natural biomolecules. One other advantage of the polymeric matrix, characteristic of MIPs, is their powerful combination with micro and nanotechnologies to create biochips.Here, we present recent approaches developed in our groups to pattern MIPs at micro and nanoscale. First, Micropatterning tools were developed and referenced as contact and non-contact techniques. Contact method is based on array of silicon cantilevers fabricated by micromachining techniques and mounted on a three-stage automated spotter. This resulted in arrays of MIPs serially and precisely localized on a substrate, with resolution down to 20µm. Alternatively, a parallel approach was initiated by taking benefit of photopolymerization of MIPs to create patterns by photolithography. After spin-coating prepolymers, reticulation was initiated using a mask and resulting MIPs were in a wide variety of features with a resolution down to 1.5µm. By repeating sequentially deposition and local polymerization, a multi-array approach was also introduced. Final objective using these techniques is to compare performances of resulting MIPs in terms of sensitivity, integration, mass production and versatility.More recently, evolution of nanotechnologies made possible to engineer nanostructures. Main issues concern high throughput screening and testing with enhanced sensitivity by increasing the surface area of the MIP material. In this field, soft lithography and nanowires approaches are of major interest since they allow producing nanopatterns with high aspect ratio. Both methods succeeded to create MIPs nanofeatures. Nanofilaments were produced with elevated density, resulting in a factor 40 increase of the surface area compared to a flat surface. These conditions favored accessibility to binding sites and in molecular recognition assays, sensitive levels of detection were reached. A similar behavior was also observed when MIPs were patterned by soft lithography. Features were formed as a network of nanolines of 500nm wide and 400µm long with a pitch of 1µm, covering a large area of 400x400µm2. Thanks to developed techniques, we will conclude on perspectives on MIPs micro and nanopatterns as efficient alternatives to create advanced biochips.
10:00 AM - **VV1.5
Bioinspired Inorganic/polymer Thin Films.
G. Hirata 1 , S. Diaz 2 , P. Chen 2 , M. Meyers 2 , Joanna McKittrick 1 Show Abstract
1 Mechanical and Aerospace Engineering Department, University of California, San Diego, La Jolla, California, United States, 2 , Center for Nanoscience and Nanotechnology-UNAM, Ensenada Mexico
Studies of hard biological materials such as marine shells, animal teeth, horns and bones have produced fascinating ideas for mimicking their micro/nanostructure in the lab. In this work we have analyzed the morphology ad mechanical properties of the nacreous portions of red abalone shells by SEM, TEM, XRD and the chemical compositions by EDS and ESCA. Bioinspired laminates were fabricated as multi-layers of several biocompatible materials: CaCO3 (aragonite)/polymer, ZrN/polymer and ZrO2/polymer for various polymer compositions, by using a combination of dc magnetron sputtering and pulsed laser deposition on glass, quartz and silicon substrates. Substrate temperatures for film deposition were varied in the range of 25-115°C. The films are composed of nanocrystalline or amorphous particles with different degrees of porosity as observed by TEM and AFM. High resolution TEM analysis at the inorganic/organic interface revealed well formed inorganic films which are separated by the polymeric layer (10-50 nm). The hardness values showed an increase for the inorganic film/polymer stacked system as compared with the single film. A more detailed analysis of the results together with AFM/nanoindentation measurements will be presented. This research is supported by ARO Grant W911F-08-1-0461 and NSF Grant DMR 0510138.
10:30 AM - VV1.6
Bio-electrospray Validation from Cells to Organism.
Suwan Jayasinghe 1 Show Abstract
1 Mechanical Engineering, University College London, London United Kingdom
Tissue engineering is a field of interdisciplinary sciences being extensively researched as it is a promising and possible solution for organ transplantation. Various biomaterials and cell-seeding techniques have been developed to construct 3-D tissue in the laboratory. However, many problems of seeding cells in 3-D scaffolds pose several challengers. Thus there are numerous approaches invented with regards to handling cells directly. Our technique, bio-electrospray (BES), has been developed to be able to manipulate cells and materials simultaneously. The method was proved that it is feasible to directly jet cells at high concentration without affecting cell viability. Moreover, in this study, cell functions were investigated and presented to assure the possibility of using BES as a strategy for tissue engineering. Hence stem cells (MSC), primary cells (blood) and whole organism (C. elegans) were used to assess their associated biologics post treatment. The metabolic assay result of electrosprayed MSC have shown the same propagation efficiency along 3 days as controls. Cell viabilities, apoptosis by key enzyme assays during 24 hours after jetting and necrosis by PI staining, subsequent FACS scan after jetting, were also investigated. No significant numbers of cell deaths were investigated. Additionally, gene expressions by RT-qPCR on whole blood cells were observed by 13 specific primers to both specific and constitutive genes. Genetic level was reported as delta Ct for 78 cross comparisons. No differences of gene expression among sprayed and non-sprayed samples were observed. Finally the embryo of C. elegans were treated and examined for productivity, heat shocked response and global gene expressions. Brood size experiments have confirmed the egg laying capacity of electrosprayed samples are as efficient as the control, no GFP activation of heat shock responses as well as no significant differences in gene expressions have identified. These experiments have confirmed that BES is capable of directly handling cells for tissue engineering without perturbing viability, proliferation and gene expression. We are currently running tissue creation by using BES to position cells for controllable cell patterning for possible organ construction.
10:45 AM - VV1.7
Nano- and Micro-Scale Adhesion in Drug-eluting Stents.
Ting Tan 1 , Juan Meng 1 , Nima Rahbar 2 , Hannah Li 3 , George Papandreou 3 , Cynthia Maryanoff 4 , Winston Soboyejo 1 Show Abstract
1 , Princeton University, Princeton, New Jersey, United States, 2 , University of Massachusetts Dartmouth, North Dartmouth, Massachusetts, United States, 3 , Cordis Corporation, Warren, New Jersey, United States, 4 , Cordis Corporation, Spring House, Pennsylvania, United States
This paper presents the results of a combined experimental and theoretical/computational study of nano- and micron-scale adhesion and interfacial fracture in drug-eluting stents (DES). We have previously published the development of an atomic force microscopy (AFM) method to quantify the adhesion forces between and cohesive forces within the layers of a drug-eluting stent (DES). Surface pairs representing both the individual components and the complete chemistry of each layer within the DES were prepared, and measurements of the pull-off forces between coated AFM tips and substrates were obtained to evaluate all possible interactions occurring in the DES structures. As a model, the CYPHER® Sirolimus-eluting Coronary Stent was studied. A combination of adhesion theory and fracture mechanics concepts was then used to obtain estimates of the mode I fracture toughness values. The experimental measurements of the mode mixity dependence of interfacial fracture toughness were shown to be consistent with crack-tip shielding estimates from zone/row fracture mechanics models.
11:00 AM - VV1.8
Localized and Sustained Release from Drug-Loaded Implantable Devices.
Dattatri Nagesha 1 , Evin Gultepe 1 , Robert Cormack 2 , Mike Makrigiorgos 2 , Srinivas Sridhar 1 Show Abstract
1 Physics, Northeastern University, Boston, Massachusetts, United States, 2 Radiation Oncology, Dana Farber Cancer Institute, Boston, Massachusetts, United States
There are a number of biomedical implants that are used today that are capable of localized drug delivery for improved therapy, enhanced tissue adhesion, decreased immune response and biocompatibility. Non-erodible surfaces especially nanoporous alumina and titania have been used for improved drug loading and release capabilities. However, there is a poor understanding on the elution kinetics of drugs from within these nanoporous surfaces. To study this, nanoporous alumina templates with precise control on pore size, distribution and height was fabricated by anodization method. Templates were loaded with fluorescent Doxorubicin (Dox) as the model drug molecule and release of Dox was monitored using in-situ fluorometry. After an initial burst release phase during the first 100 minutes, which follows non-Fickian diffusion, a long time sustained release followed for several weeks. Constructing a model for sustained release kinetics show that activated surface densities dependent desorption was in effect for nanoporous templates. In localized drug delivery from drug-loaded implants from within tumor sites there is lack of theoretical modeling to predict drug distribution and diffusion upon release. This was studied using drug-loaded polymer coatings on gold fiducial markers. Currently, these markers are used to increase spatial accuracy in delivering radiation treatment for cancer therapy. Elution of drugs locally from these fiducials from within the tumor can further enhance their role as a treatment modality. Results from the modeling study of drug diffusion and in vitro drug release experiments from these fiducials will be discussed in this presentation. This work was supported by IGERT Nanomedicine Science and Technology Program (NSF 0504331), Dana Farber Cancer Institute and Northeastern University
11:15 AM - VV1.9
Effect of Processing Conditions on the Microstructure and Sirolimus Elution from Poly (lactide-co-glycolide) Films.
Andrew Ro 1 , Robert Falotico 1 , Vipul Dave 1 Show Abstract
1 Therapeutics and Advanced Research, Cordis Corporation, Johnson and Johnson, Warren, New Jersey, United States
Supercritical carbon dioxide is a viable solvent to process drug-containing polymer devices for drug delivery. It can also be used to modify the morphological features of both polymer and drug at mild temperatures, which presents a prospect to tune drug release and degradation of the device. Poly (L-lactide-co-glycolide) (PLLGA) and poly (DL-lactide-co-glycolide) (PDLGA) films containing sirolimus were prepared using a solution-casting method. Various combinations of processing parameters (e.g. temperature and pressure) were used during supercritical CO2 extraction in order to remove residual solvent and to obtain various polymer and drug morphologies. The morphological features of polymer and drug were characterized by x-ray scattering and differential scanning calorimetry. A range of polymer and drug crystallinities were obtained and the resultant morphologies were dependent on supercritical CO2 extraction conditions and the stereochemistry of the polymer. Heat of fusion values for the polymers ranged from 0 to 40 J/g and the values correlated with the stereoregularity of PLGA. The drug phase in the PLGA films exhibited heat of fusion values ranging from 7 to 46 J/g and was dependent on the chemistry of the PLGA matrix and processing conditions. Surface features of the sirolimus-containing films were analyzed using electron microscopy. Depending on the physical properties of the polymer and drug, the sirolimus-containing PLGA films exhibited unique drug release profiles and in vitro degradation behavior. Crystallinity and stereochemistry of the PLGA matrix were significant determining factors for drug diffusion kinetics.
11:30 AM - VV1.10
Unique Mechanical Properties from Melt Processing Polylactide.
Jianbin Zhang 1 , SuPing Lyu 1 , Lian Luo 1 , Byrant Pudil 1 , Jim Schley 1 , Mike Benz 1 , Adam Buckalew 1 , Kim Chaffin 1 , Chris Hobot 1 , Randy Sparer 1 Show Abstract
1 Medtronic Strategy and Innovation, Medtronic, Minneapolis, Minnesota, United States
Poly(lactide) (PLA) and its copolymers can degrade through hydrolysis to non-toxic and water soluble metabolic products. They are ideal materials for biomedical applications like drug delivery, tissue engineering, orthopedics, and etc. However, these polymers are brittle and often need to be toughened. One of the most effective toughening methods is reactive blending. In this paper, we reported unique mechanical properties created by dispersing poly(trimethylene carbonate) (PTMC) in poly(lactide-co-glycolide) (PLGA) on the nanometer scale through reactive blending at high temperature. We speculated that the reaction was a transesterification reaction between the two polymers, which late was proven to be true by a model experiment. A fluorescence-labeled PTMC was designed in such a way that it can be used to detect the reaction between polymers if there is any. After melt-blended the fluorescence-labeled PTMC into the PLGA, the molecular weight results demonstrated the formation of PTMC-PLGA copolymers. We demonstrated that these in situ formed copolymers not only make it feasible for the PTMC phase to form stable nanometer-scale dispersion in the PLGA, it was also required for improved interfacial mechanical performance. This was demonstrated by another experiment where scanning electron micrographs showed that the interfacial adhesion between PLGA/PTMC in a melt-mixed blend was strong and the PTMC dispersed particles stayed at cryo-fractured surfaces.
11:45 AM - VV1.11
Laser Processing of Functional Microstructured and Nanostructured Biomaterials.
Roger Narayan 1 , Ashok Kumar 2 Show Abstract
1 Biomedical Engineering, University of North Carolina, Chapel Hill, North Carolina, United States, 2 Mechanical Engineering, University of South Florida, Tampa, Florida, United States
Lasers may serve to create novel biomaterials with unique biological functionalities. We have recently developed microstructured and nanostructured biomaterials with unique biological functionalities using pulsed laser deposition and laser direct writing processes. For example, lasers have recently been used to fabricate biomaterials with unusual cell compatibility and blood compatibility properties. Chemical, mechanical, and biological properties of these laser-processed materials will be discussed.
12:00 PM - **VV1.12
Structure-property linkages in hierarchically structured hybrid biomaterials
Ulrike Wegst 1 Show Abstract
1 Materials Science and Engineering, Drexel University, Philadelphia, Pennsylvania, United States
One of the major challenges in Tissue Engineering is to develop custom-designed scaffolds, tailored to mimic natural biological templates and designed to actively regulate cell differentiation and tissue assembly. Shortcomings of current tissue scaffolds are that they are chemically, structurally and mechanically very different from the natural tissue for which they substitute. Most current bone substitute materials, for example, are monolithic. This is in contrast to natural bone and other biological ceramics such as, dentin, enamel and mollusk shell which are composites and achieve their unique property combination due to their hierarchical structure. A promising route for the synthesis of tissue substitute materials thus seems to be the emulation of tissue’s hybrid structure because this will allow us to custom-design the materials through variations in composition and structure so that it can simultaneously and optimally fulfill biological and mechanical requirements. We systematically develop hierarchically structured composites that are tailored and optimized in their structural, mechanical, and chemical properties for tissue engineering applications. Preparing tissue scaffolds by freeze-casting (“ice-templating”) of polymers, ceramics and composites we have careful control of material composition and architecture at several length scales of their hierarchical microstructure. This enables us to prepare scaffolds for both hard and soft tissue applications and to deliver the required unique combination of properties necessary for successful tissue replacement.
12:30 PM - VV1.13
Microfabrication of Asymmetric, Homogenous Cell-laden Hydrogel Microcapsule.
Tram Dang 1 , Qiaobing Xu 1 , Kaitlin Bratlie 1 3 , Esther O'Sullivan 4 , Xiao Chen 1 , Robert Langer 1 2 , Daniel Anderson 2 Show Abstract
1 Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States, 3 Department of Anesthesiology, Children Hospital Boston, Cambridge , Massachusetts, United States, 4 Islet Transportation and Cell Biology, Joslin Diabetes Center - Harvard Medical School, Boston, Massachusetts, United States, 2 David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge , Massachusetts, United States
Cell encapsulation has been broadly investigated as a technology to provide immunoprotection for transplanted endocrine cells. Here we develop a new fabrication method that allows for rapid, homogenous microencapsulation of insulin-secreting cells with varying microscale geometries and asymmetrically modified surfaces. Micromolding systems were developed using polypropylene mesh, and the mesh material/surface properties associated with efficient encapsulation were identified.Cells encapsulated using these methods maintain desirable viability and preserve their ability to proliferate and secrete insulin in a glucose-responsive manner. This new cell encapsulation approach enables a practical route to an inexpensive and convenient process for the generation of cell-laden microcapsules without requiring any specialized equipment or microfabrication process.
12:45 PM - VV1.14
Novel Encapsulation Strategies Designed for Block Copolymers.
Conlin O'Neil 1 , Diana Velluto 1 , Andrija Finka 2 , Davide Demurtas 3 , Jeffrey Hubbell 1 Show Abstract
1 Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Vaud, Switzerland, 2 Department of Plant Molecular Biology, University of Lausanne, Lausanne, Vaud, Switzerland, 3 Center for Integrative Genomics, University of Lausanne, Lausanne, Vaud, Switzerland
Although block copolymers have been under intense investigation for decades, it was not until recently with the development of biodegradable chemistries such as hydrolysis, oxidation, and reduction sensitive materials that these systems could be fully exploited as drug carriers. Conventional methods to load therapeutic small molecule drugs or proteins into block copolymer micelles, worm like micelles or polymersomes were originally developed for use with liposomes, emulsions, or small molecule natural and synthetic amphiphiles. However, conventional methods such as solvent dispersion or thin film hydration do not always yield optimal results. Recently, our group has explored the use of block copolymers composed of poly(ethylene glycol)-bl-poly(propylene sulfide) (PEG-PPS), towards drug delivery. For some therapeutic compounds, conventional methods yield high encapsulation efficiencies such as for rapamycin (89% efficiency at 16% loading), or ADAMTS-5 inhibitor (~100% efficiency at 16% loading). However for other small molecule therapeutics, these methods yielded poor results, such as for paclitaxel (4% efficiency at 1% loading). To improve the encapsulation efficiency, an entirely new process was applied which we are calling “direct hydration”. In this process, the neat paclitaxel is heated at 95C for 15-20 minutes with a small molecular weight polyethylene glycol and PEG-PPS. After the melt cools to room temperature, the formulation is rehydrated with an aqueous buffer and this yields loaded micelles displaying high encapsulation efficiencies (88% efficiency at 14% loading for paclitaxel). For cyclosporin A we obtained good results using solvent evaporation from dichloromethane in water (61% efficiency at 3% loading). However we wanted to develop a solvent free method to encapsulate the drug due to concerns over residual solvent. We found that heating the cyclosporin A in the presence of PEG-PPS micelles in water at 60C with stirring partitioned most of the compound into the micelles (73% efficiency at 5% loading). We have also recently been investigating the encapsulation of proteins using the direct hydration method. Here we use PEG-PPS which typically forms polymersomes. The protein of interest can be dispersed into the formulation, encapsulating it inside the aqueous core of the polymersomes. Using this method, we have encapsulated ovalbumin at 37%, bovine serum albumin at 19%, and bovine γ-globulin at 15% efficiency. These numbers represent a substantial improvement over conventional thin film hydration which typically yields efficiencies < 10%.In this presentation I will discuss these new methods and their implications for drug delivery for the next generation of polymeric self-assembling systems.
VV2: Microstructured and Nanostructured Biomaterials
Tuesday PM, December 01, 2009
Room 202 (Hynes)
2:30 PM - **VV2.1
Engineering of Micro- and Nano-Scale Materials to Control Cell Morphology.
Michael Bucaro 1 , Benjamin Hatton 1 , Joanna Aizenberg 1 Show Abstract
1 , Harvard University, Cambridge, Massachusetts, United States
Smart biomaterials that can actively guide cell form and fate will enable new solutions in regenerative medicine. We describe a strategy to create multifunctional, actuatable, cell-biomaterial interfaces based on nanopillar arrays. Morphological characteristics of uncommitted cells were manipulated by tailoring the length and distribution of nanostructures. Nanopillar geometries were identified that induce neuron-like morphologies in undifferentiated cells. The results demonstrate the use of conventional silicon fabrication methods to create tunable nanobiomaterials capable of eliciting a spectrum of morphological characteristics and patterned growth in pluripotent cells. This approach is compatible with integrated circuit fabrication and could be applied to create bioinductive surfaces that probe and direct cell behavior, for example, in the formation of cellular networks on neural chips, stem cell lineage specification and manipulation of cell activity for a variety of biomedical applications.
3:00 PM - VV2.2
Biomaterials Nano Geometry for Control of Stem Cell Differentiation.
Karla Brammer 1 , Seunghan Oh 1 2 , Sungho Jin 1 Show Abstract
1 Materials Science & Engineering, UC San Diego, La Jolla, California, United States, 2 College of Dentistry, Wonkwang University, Iksan Korea (the Republic of)
Two important goals in stem cell research are to control the cell proliferation without differentiation, and also to direct the differentiation into a specific cell lineage when desired. Recent studies indicate that the nanostructures substantially influence the stem cell behavior. It is well known that mesenchymal stem cells (MSCs) are multipotent stem cells that can differentiate into stromal lineages such as adipocyte, chondrocyte, fibroblast, myocyte, and osteoblast cell types. By examining the cellular behavior of MSCs cultured in vitro on nanostructures, some understanding of the effects that the nanostructures have on the stem cell’s response has been obtained. Here we demonstrate that TiO2 nanotubes produced by anodization on Ti implant surface can regulate human mesenchymal stem cell (hMSC) differentiation towards an osteoblast lineage in the absence of osteogenic inducing factors. Altering the dimensions of nanotubular-shaped titanium oxide surface structures independently allowed either augmented human mesenchymal stem cell (hMSC) adhesion at smaller diameter levels or a specific differentiation of hMSCs into osteoblasts using only the geometric cues. Small (~30 nm diameter) nanotubes promoted adhesion without noticeable differentiation, while larger (~70 - 100 nm diameter) nanotubes elicited a dramatic, ~10 fold stem cell elongation, which induced cytoskeletal stress and selective differentiation into osteoblast-like cells, offering a promising nanotechnology-based route for novel orthopaedics-related hMSC treatments. The fact that a guided and preferential osteogenic differentiation of stem cells can be achieved using substrate nanotopography alone without using potentially toxic, differentiation-inducing chemical agents is significant, which can be useful for future development of novel and enhanced stem cell control and therapeutic implant development.1. Seunghan Oh, et al, J. Biomed. Mater. Res. 78A, 97 (2006).2. Seunghan Oh, et al, PNAS 106(7), 2130 (2009).
3:15 PM - VV2.3
The Wear Properties of Ultra High Molecular Weight Polyethylene (UHMWPE) for applications to Metal-on-UHMWPE Total Hip Replacement against Ti Composite Layers produced by Plasma-Spraying.
Seung-mok Cho 1 2 , Hyun-Kwang Seok 1 , Seung-hee Han 1 , Jin-Woo Park 2 , Yu-Chan Kim 1 Show Abstract
1 Materials science & technology research division, Korea Institute of Science & Technology, Seoul Korea (the Republic of), 2 Department of Materials Science & Engineering, Yonsei University , Seoul Korea (the Republic of)
We present titanium composite coating layers with excellent wear properties produced by plasma-spraying process for applications to artificial hip joints. Using the Ti composites coatings, the wear rate of ultra high molecular weight polyethylene (UHMWPE) in metal-on-UHMWPE total hip replacement is reduced significantly compared to Co alloy coatings that have been most extensively used. The Ti coating layers are produced in controlled atmospheres of Ar or N2 in a chamber. Under N2 atmosphere, coating layers with laminated Ti and TiN layered structures are produced and the wear properties are better than the coatings under Ar atmosphere. To evaluate the wear properties, pin-on-disk type wear tests of UHMWPE against the Ti composite coatings with various thicknesses and different microstructures are performed in bovine serum lubrication. The microstructures of the coatings are analyzed using scanning electron microscopy (SEM) and Auger electron spectroscopy (AES). Hardness and surface roughness are analyzed by nano-indentation and atomic force microscopy (AFM), respectively. Based on the analysis results, the different wear mechanisms of the various coatings are discussed. Finally, biocompatibility of coating layers are evaluated under ISO 10993-1, ISO 10993-5 standards.
3:30 PM - VV2.4
Fabrication of (Ti-O-N-Si)/Ti Composite Coating on NiTi Shape Memory Alloy Using PIIID and Coating Evaluation.
Tao Sun 1 , Lang-Ping Wang 2 , Min Wang 1 Show Abstract
1 Mechanical Engineering, The University of Hong Kong, Hong Kong China, 2 Materials Science and Engineering, Harbin Institute of Technology, Harbin China
NiTi shape memory alloys (SMAs) are attracting increasing attention in orthopedics and dentistry due to their unique properties of shape memory and superelasticity. But problems such as bioinertness, Ni ion release and wear debris generation have prevented them from wide applications in the medical field. Appropriate surface modification of NiTi SMAs can eliminate or minimize these problems and provide the new scope of medical applications for these materials. Various techniques have thus been investigated for the surface modification of NiTi SMAs and these techniques have their respective advantages and disadvantages. In this investigation, to achieve a good combination of bioactivity, biocompatibility and wear resistance, thin (Ti-O-N-Si)/Ti composite coatings were fabricated on a NiTi SMA (50.8 at.% Ni) by using a combination of the plasma immersion ion implantation and deposition (PIIID) technique and the radio frequency (RF) magnetron sputtering technique. PIIID, which avoids the “line-of-sight” problem encountered by many coating techniques for metal implants, can produce coatings on the surface of implants of complex shapes and the coatings formed possess high adhesion strength. For obtaining (Ti-O-N-Si)/Ti composite coatings, a Ti layer was fabricated first on NiTi SMA in order to improve the adhesion strength of the composite coatings. Subsequently, O2 and N2 plasma were generated simultaneously in the PIIID equipment and a Ti-O-N layer formed on the Ti layer. Finally, Si was introduced into the Ti-O-N layer through RF magnetron sputtering. After coating fabrication, the structure and properties of composite coatings were studied. XRD results showed that there were no diffraction peaks corresponding to TiO2 or TiN for (Ti-O-N-Si)/Ti composite coatings, indicating that after the coating fabrication process, TiO2 and TiN were not formed in the coatings. SEM examination of coating surfaces and cross-sections indicated that (Ti-O-N-Si)/Ti composite coatings were uniform and compact, having thickness values of about 1μm to 1.5μm. EDX elemental mapping of coating cross-sections indicated that Ni element was depleted from the surface. Pin-on-disc wear tests showed improved wear resistance of NiTi SMA with the (Ti-O-N-Si)/Ti composite coating. Potentiodynamic polarization tests indicated greatly enhanced corrosion resistance of (Ti-O-N-Si)/Ti coated NiTi SMA. The wettability and bioactivity of NiTi SMA with and without the (Ti-O-N-Si)/Ti coating were also evaluated by contact angle measurement and by incubation for two weeks in a simulated body fluid, respectively.
3:45 PM - VV2.5
Localized Corrosion of Surface Treated Porous Nitinol in Different Corrosion Liquid Media.
Chandan Pulletikurthi 2 1 , Norman Munroe 2 1 , Puneet Gill 2 1 , Waseem Haider 2 1 , Smit Pandya 2 1 Show Abstract
2 Applied Research Center, Florida International University, Miami, Florida, United States, 1 Materials Science and Engineering, Florida International University, Miami, Florida, United States
Implantable materials are designed to survive in a complex biological medium which consists of a variety of proteins, amino acids, metal and hydrogen ions. As a result, there is always grave concern with regard to the biocompatibility and corrosion resistance of such materials. In this research localized corrosion tests were conducted on surface treated Porous Nitinol (PNT) in osteoblast cell culture medium at 37 °C in order to simulate a bone