Suwan Jayasinghe, University College London
Mallika Kamarajugadda, Medtronic, Inc.
Roger Narayan, University of North Carolina at Chapel Hill and North Carolina State University
Antoni Tomsia, Lawrence Berkeley National Laboratory
Symposium Support Applied Physics Reviews|AIP Publishing
M2: Advanced Polymers and Ceramics for Biomedical Applications
Monday PM, November 30, 2015
Sheraton, 2nd Floor, Liberty B/C
2:30 AM - *M2.01
Morphological Studies of Polymer Films and Formulations for Oral Drug Delivery Applications
Vipul Dave 1 Gerard McNally 1
1Johnson amp; Johnson Consumer Inc. Ft Washington United StatesShow Abstract
Different types of polymers and processes are utilized to prepare pharmaceutical formulations to achieve the desired drug delivery attributes from solid oral dosage forms. In this study, selected pharmaceutical grade polymers and additives were utilized to prepare films and coated formulations using different techniques. Experiments were performed to characterize the bulk and surface properties of the materials to gain insights into the functionality of the polymers. Examples of the methods that were utilized to characterize the materials included Thermogravimetric Analyzer (TGA) combined with an Infrared Spectrometer (TG-IR), X-ray diffraction, dynamic vapor sorption (DVS), Time-of-Flight Secondary Ion Mass Spectrometry (TOF-SIMS), and Confocal Raman Spectroscopy. Special emphasis was given to study the effect of moisture and plasticizers on the physical properties of the films and formulations. Selected formulations were developed to prepare solid oral dosage forms containing different active pharmaceutical ingredients. The presentation will provide a summary of the results obtained from characterizing the films, coated formulations and drug delivery dosage forms.
3:00 AM -
3:15 AM - *M2.03
Towards Computer-Aided, Rational Design of Ceramic Biomaterials: Combining Micro-Computed Tomography, Nanoindentation, Ultrasonic, and Micromechanical Theory
Christian Hellmich 1
1TU Wien - Vienna Univ of Technology Vienna AustriaShow Abstract
Biomaterials have been characterized by an ever increasing collection of highly advanced experimental techniques, while consistent and integrative evaluation of all related test results remains a significant, largely unmet challenge. As a remedy, we here present several recent activities.
We start with a new evaluation method (Czenek et al, J Mat Res 29, 2757ff., 2014), which uses the unique linear relationship between gray values and X-ray attenuation coefficients, together with the energy-dependence of the latter, to identify (i) the average x-ray energy used in the CT device, (ii) the X-ray attenuation coefficients, and (iii), via the x-ray attenuation average rule, the intravoxel composition, i.e., the microporosity, which, amongst others, governs the voxel-specific mechanical properties, such as stiffness and strength. The method is realized for six 3D tricalcium phosphate scaffolds, seeded with pre-osteoblastic cells and differentiated for 3, 6, and 8 weeks, respectively. The corresponding voxel-specific microporosities turn out to increase during the culturing period (resulting in reduced elastic properties, as determined from micromechanical considerations), while the overall macroporosity remains constant.
As a second example, consistent combination of nanoindentation, ultrasound, and micromechanics theory is shown by example of porous baghdadite (Ca3ZrSi2O9) scaffolds (Kariem et al, Mat Sci Eng 46C, 553ff., 2015). The resulting porosity-stiffness relations further confirm a formerly detected, micromechanically explained, general relationship for a great variety of different polycrystals (Fritsch et al, J Appl Mech 80, 020905-1, 2013),which also allows for estimating the zero-porosity case, i.e. Young modulus and Poisson ratio of pure (dense) baghdadite. These estimateswere impressively confirmed by a physically and statistically independent nanoindentation campaign comprising some 1750 indents. Consequently, we can present a remarkably complete picture of porous baghdadite elasticity across a wide range of porosities, and, thanks to the micromechanical understanding, reaching out beyond classical elasticity, towards poroelastic properties, quantifying the effect of pore pressure on the material system behavior.
The new methods are expected to further foster the development of a rationally based and computer-aided design of biomaterials and tissue engineering scaffolds.
4:15 AM - *M2.04
Sensing the Swell
Aoife Morrin 1
1Dublin City Univ Dublin IrelandShow Abstract
Hydrogels are three-dimensional networks of polymer that have great ability to imbibe exceptionally large volumes of water. The water uptake and hence swelling of hydrogels can be controlled and manipulated depending on hydrogel design. As such, their swelling can be exploited in sensing and controlled release platforms, with applications varying from providing a simple inert protective sensor coating, to use as an intelligent drug delivery system capable of sensing physiological changes and auto-titrating a drug. This presentation will describe the work we are doing on responsive hydrogel materials, their design, and applicability to both sensing and controlled release. The context of the work will be discussed within the application area of epidermal sensing, e.g., monitoring skin barrier function.
In relation to the hydrogel-based sensing platform, electrochemical impedance spectroscopy is used to sensitively track the swelling responsive of pH-sensitive hydrogels. Indeed, the demonstration of this system for glucose detection at the sub-micromolar levels opens up the possibility of glucose detection in sweat. Electrically-stimulated drug release from these hydrogels that are composited with reduced graphene oxide will also be discussed. Finally, our recent work on the fabrication of super-macroporous structures of these hydrogels and the dramatic influence of this induced structure on the material&’s swelling behaviour and hence its sensing characteristics will be presented.
4:45 AM - M2.05
Oscillatory Shear Injection for Improved Surface Nanoimprint Processing of Biopolymers for Tissue Scaffold Applications
Graham L. W. Cross 1 2 Owen Brazil 1 Daniel J Kelly 1
1Trinity College Dublin Dublin Ireland2Adama Innovations Dublin IrelandShow Abstract
Nanoimprint lithography (NIL) is a rapid, low cost mechanical technique to create nanoscale to microscale patterns across large surface areas. Although originally introduced as a potential next generation lithography for the semiconductor industry, the technique has found itself applied in a variety of applications including biomaterials and devices. Its advantage over other techniques is to be able to provide fully deterministic surface patterning, including pattern gradients and multiscale features, in a wide variety of materials. In this work we report on a new development to improve nanoimprint processing to provide both topographical and chemical function to current and potential future tissue scaffolding polymers.
In small amplitude oscillatory shear forming (SAOSF) , a small amplitude cyclic shear displacement (up to 10&’s of nm) is applied to a rigid die in contact with a soft solid film leading to a plastic-ratchet forming action (Fig. 1). As with conventional nanoimprint, nano-feature fidelity and registry are achieved, however the technique also has advantages of constant low temperature processing and hence a wide choice of materials. For solid films, the underlying mechanism of SAOSF is due to a combination of uniformly plasticizing contacted areas of the film while simultaneously activating a novel pumping action involving die-geometry-induced broken circulation of elastoplastic flow. Crucially, the process is scale independent for thin film planar imprint, since only a critical shear strain is required. A minimal applied normal load largely eliminates elastic distortions thought to be responsible for residual layer non-uniformity and other replication defects common to imprint. Finite element simulations of the process with simple elastic-elastoplastic materials agree well with experimental observations.
In this work we demonstrate the successful application of SAOSF to large area surfaces and thin films of the biodegradable polymer PLGA. Imprint dies with nanoscale patterns were imprinted with high fidelity across cm scale areas at temperatures below above and below the glass transition, greatly reducing biopolymer-die adhesion and thus increasing die lifetime, as well as reducing overall imprint time due to a short thermal cycle. We demonstrate the efficacy of this technique in influencing stem cell response to surface patterns. While currently implemented in conventional hot embossing and nanoimprint setups, steps toward adapting the approach high throughput to roll-to-roll processing will be described, including a lamination strategy allowing fully 3D porous tissue scaffolds to be fabricated with complete determinism of internally patterned surfaces. The advantages that SAOSF provides may become particular great in the continuous processing environment.
 G. L. W. Cross, B. S. O'Connell, H. O. Ozer and J. B. Pethica, Nano Lett. 7, 357 (2007).
5:00 AM - M2.06
Fabrication of Polymer Coated Microparticles with Low Permeability
Li Zhao 1 Julien Gautrot 1 Gleb Sukhorukov 1
1Queen Mary University of London London United KingdomShow Abstract
Low permeability is one of the key challenges that exists in the area of drug delivery system. Due to the nature of polymers, micro drug carriers made of polymers are usually porous which leads to the failure of retaining small molecules and narrows the applications of the polymeric micro containers. Thus, our group has been trying to overcome this shortage.
In this work, low permeable Poly(methyl methacrylate) shells which are not permeable by small molecules were fabricated via surface initiated Atom Transfer Radical Polymerization (ATRP).
The kinetics of PMMA brush growth was first studied on flat substrates on which the pre-synthesized macroinitiator was deposited using Layer-by-Layer technique. The thicknesses of the PMMA films were measured with ellipsometer. The surface hydrophobicities of different substrates with and without PMMA layer were then compared by measuring the water contact angles. Increased surface hydrophobicity was witnessed from the significantly increased water contact angle on the surface with PMMA monolayer.
Further to this, low permeable PMMA shells were synthesized on the surface of CaCO3 templates from the pre-deposited macroinitiators via ATRP polymerization. Fourier Transform Infrared Spectroscopy (FTIR) and Thermogravimetric Analysis (TGA) spectrums showed that PMMA was successfully coated on the inorganic cores. Transmission Electron Microscope (TEM) was applied to observe the thicknesses of PMMA shells and they were found to be nearly in accordance with the kinetics on planar surfaces. The results of the Energy-dispersive X-ray Spectroscopy (EDS) together with those obtained from Scanning Electron Microscope (SEM) and TEM demonstrated that there were no differences in the element compositions as well as surface and inner structures of PMMA coated particles before and after ethylenediaminetetraacetic acid (EDTA) treatment. This indicates that PMMA shells are non-permeable to the dissolution agent, which has low molecular weight.
After having proven that hydrophobic polymer shells synthesized by “brush growth” technique are able to form low permeable micro containers, the same strategy was applied to fabricate the low permeable and biodegradable Poly(lactic acid) microcapsules, the properties of which are being investigated. We believe that our work could contribute to the biomedical applications.
5:15 AM - M2.08
Inkjet Printing of Materials for Drug Delivery
Roger Narayan 1
1North Carolina State University Raleigh United StatesShow Abstract
Piezoelectric inkjet printing is a materials deposition technique that relies on pressure waves from a piezoelectric actuator to precisely pattern picoliter volumes of liquids onto a surface. We have recently utilized this approach for modifying the surfaces of microneedles, which are microscale projections that may be used for transdermal delivery of many types of pharmacologic agents. Precise patterning of several pharmacologic agents was demonstrated. The mechanical and chemical properties of the inkjet-modified devices with compared against those of the unmodified devices. In addition, the functionality of the inkjet-printed drugs was validated using in vitro assays. The results suggest that piezoelectric inkjet printing is an appropriate approach for incorporating pharmacologic agents within medical devices since it is associated with rapid processing times, low cost, and facile scalability.
5:30 AM - M2.09
Mimicking Calcareous Dinoflagellate Cysts for Core-Shell Microcapsules
Archana Lovett 1 Richard Saballos 1 Mark Bewernitz 1 2 Laurie Gower 1
1University of Florida Gainesville United States2Blue Planet- ltd Los Gatos United StatesShow Abstract
Dinoflagellates are protists, mostly found as marine plankton. Some species produce a calcareous shell around their exterior as a cyst for protection during the dormant, zygotic stage of their life. Using this core-shell architecture as an inspiration, we have developed a methodology for encapsulating “soft” liquid droplets within a “hard” mineral shell. The polymer-induced liquid-precursor (PILP) mineralization process was used to deposit a calcium carbonate (CaCO3) mineral shell on the surface of surfactant-stabilized fluidic particles comprised of either oil-in-water emulsion droplets or liposomes. Size and morphological analyses were performed by various microscopic techniques, where it was observed that the PILP droplets preferentially adsorb to anionic surfactants/lipids that stabilize the suspension, and due to their liquid-like character, coalesce to form a smooth and continuous mineral coating. The processing conditions for forming these CaCO3-coated microcapsules are benign, so they can encapsulate virtually any active agent of interest. For example, hydrophobic compounds can be dissolved in oil-in-water emulsions, while hydrophilic and/or hydrophobic compounds can be dissolved within liposomes, which can then be coated with the CaCO3 mineral shell. Confocal microscopy was used to demonstrate an oil-soluble fluorescent dye is encapsulated in the interior of the emulsion, or both hydrophilic and hydrophobic compounds can be incorporated with the aqueous and hydrocarbon regions of liposomes, respectively. The metastable morphology of the CaCO3 shell enables a pH dependent degradation of the particles, allowing for release of the active agent of interest. These CaCO3-coated microcapsules can be dried down to a powder, while retaining the active agent within the fluidic core, thereby saving in storage and transportation expenses because the large solution phase of the suspension is removed. In conclusion, while dinoflagellates utilize this encapsulation strategy as a protective shell, these biomimetic core-shell microcapsules have a myriad of potential applications because of their inherent environmentally-benign composition and biocompatibility, such as in release of pesticide or fertilizer, in chemical reactions such as release of catalyst of specific reagents, in hair/skin care products for release of conditioner or other compounds, in health care for release of pharmaceutics, or in self-healing composites for release of a sealant during capsule fracture.
M1: Nanomaterials for Biomedical Applications
Monday AM, November 30, 2015
Sheraton, 2nd Floor, Liberty B/C
9:00 AM - *M1.01
Synthesis and Characterization of Bimetallic Noble Metal Nanoparticles for Biomedical Applications
Prem C. Pandey 1
1Indian Institute of Technology(BHU) Varanasi IndiaShow Abstract
We report herein a facile approach to synthesize processable bimetallic nanoparticles (Pd-Au/Au-Pd/Ag-Au/Au-Ag) decorated Prussian blue nanocomposite (PB-AgNP). The presence of cyclohexanone/formaldehyde facilitates the formation of functional bimetallic nanoparticles from 3-aminopropyltrimethoxysilane (3-APTMS) capped respective noble metal ions under desired ratio of hetero noble metal ions. The use of aforementioned reducing agents (3-APTMS and cyclohexanone) also enables the synthesis of polycrystalline Prussian blue nanoparticles (PBNPs). As synthesized PBNPs, Pd-Au/Au-Pd/Ag-Au/Au-Ag enable the formation of nano-structured composites displaying better catalytic activity than that recorded with natural enzyme. The nanomaterials have been characterized by UV-vis, FT-IR and Transmission Electron Microscopy (TEM) with following major findings: (1) 3-APTMS capped noble metal ions in the presence of suitable organic reducing agents [3-Glycidoxypropyltrimethoxysilane (GPTMS), Cyclohexanone and Formaldehyde] are converted into respective nanoparticles under ambient conditions, (2) the time course of synthesis and dispersibility of the nanoparticles are found as a function of organic reducing agents, (3) the use of formaldehyde and cyclohexanone in place of GPTMS with 3-APTMS outclasses the other two in imparting better stability to amphiphilic nanoparticles with reduced silanol content, (4) an increase in 3-APTMS concentrations causes decrease in nanogeometry of nanoparticles (5) simultaneous synthesis of bimetallic nanoparticles under desired ratio of palladium/gold and silver/ gold cations are recorded, (6) cyclohexanone mediated synthesis nanoparticles enable the formation of homogeneous nanocomposite with PBNP as peroxidase mimetic representing potential substitute of peroxidase enzyme. The peroxidase mimetic ability has been found to vary as a function of 3-APTMS concentration revealing the potential role of functional metal nanoparticles in bioanalytical applications.
M3: Poster Session
Monday PM, November 30, 2015
Hynes, Level 1, Hall B
9:00 AM - M3.01
Influence of Laser Structured Pt/Ir Brain Implant Electrodes with Trapezoidal Cross Section on MRI Artefact Size
Johannes B. Erhardt 1 Jochen Leupold 2 Erwin Fuhrer 3 Oliver Gruschke 3 Matthias C. Wapler 1 Juergen Hennig 2 Jan Korvink 3 Thomas Stieglitz 1
1University of Freiburg Freiburg Germany2University Medical Center Freiburg Freiburg Germany3Karlsruhe Institute of Technology Karlsruhe GermanyShow Abstract
Most active implantable medical devices (AIMD) cause contraindication for implanted patients with magnetic resonance imaging (MRI) due to safety reasons (force, heating, imaging artefacts). Artefact reduction is especially relevant to enable imaging in the direct vicinity of implanted devices e.g. for postoperative placement verification and continuous checkup examinations .
Many AIMDs rely on thin film technology, where, depending on the deposition process, the edge of a structure shows various slopes. While the far-field of the magnetic distortion will just be dominated by the dipole that is proportional to the volume, the artefacts of thin films may also highly depend on edge effects. These will depend on the film thickness and at least to higher order also on the slope. While one can easily simulate the magnetic field itself, it is non-trivial how this translates into MR artefacts. Hence, we took an experimental approach to investigate this systematically at the example of Pt/Ir electrodes. For this purpose we developed a process to laser-structure trapezoidal cross sections and compared the artefact size of electrodes featuring various edge slopes.
For sample preparation, we laminated 25 µm thick Pt/Ir foil (Goodfellow) on silicone substrate. Thereafter, we used a Rapid10 picosecond-laser (Lumera) to structure 750 µm in diameter, disc shaped, electrode-like samples with trapezoidal cross section of various angles. Then, the samples underwent MRI examination in a 7 T Bruker Biospec 70/20. For comparison, we fabricated samples with the same slope angles but with constant volume (larger diameter). Finally, samples with rectangular cross section but varying thickness were investigated.
Laser ablation proved to be a reproducible method for structuring Pt/Ir discs with trapezoidal cross section and various slope angles. The MRI examination of these samples (non-constant volume) showed distinct differences in MRI artefact size. However, samples with the same slopes but constant volume showed hardly any difference in MRI artefact size. The samples with rectangular cross section and varying thickness suggested a linear dependency of volume to MRI artefact size.
We show that implant electrode structures with trapezoidal cross section can be fabricated with a laser ablation process. Furthermore, these preliminary investigations suggest that sloped edges have no significant influence on MRI artefact size, whereas the sample volume (thickness) seems crucial, as expected. We conclude, for MRI artefact reduction purposes more effort should be dedicated to reducing metal volume in implants, whereas the structure of the edges and hence the choice of manufacturing process is less critical.
Acknowledgements: This work was funded within the Cluster of Excellence “BrainLinks-BrainTools” by the German Research Foundation (DFG ExC1086).
Zrinzo et al.:WorldNeurosurgery;76(1):164-172(2011)
9:00 AM - M3.02
UV/Ozone Surface Modification for Long-Term Stable Hydrophilic Surface of Polymer Microfluidic Devices
Shogo Uehara 1 Osamu Tsuji 2
1SAMCO Inc. Sunnyvale United States2SAMCO Inc. Kyoto-city JapanShow Abstract
Polymer microfluidic devices are an emerging technology, enabling low-cost and quick clinical diagnostics. The polymer materials used in the devices are generally hydrophobic, and surface modification is required for stable flow in the micro-size channels. There are several techniques for obtaining a hydrophilic surface. Plasma surface modification, especially oxygen plasma treatment, is widely used for this application; however hydrophobic recovery quickly starts after the treatment. Therefore, it is not easy to keep the surface hydrophilic over long time periods. UV/ozone treatment is also a well-known technique for the surface modification. The disadvantage of UV/ozone treatment is that the process is more time-consuming compared to oxygen plasma treatment. Therefore, rapid and effective surface modification processes by UV/ozone treatment need to be developed.
In this presentation, we will describe parameters for rapid and effective surface modification by UV/ozone treatment and then will compare the subsequent hydrophobic recovery with oxygen plasma treatment. The polymer materials chosen in this study were: (1) polymethyl methacrylate (PMMA), (2) cyclic olefin copolymer (COC), (3) cyclic olefin polymer (COP) and (4) polyether ether ketone (PEEK). A UV/ozone cleaner (Model UV-2, SAMCO Inc.) was used for the surface modification. The system is equipped with an ozone generator for higher ozone concentration (30-160 g/m3) and a sample stage heater capable of controlling from ambient to a maximum temperature of 300°C. For evaluation of the wettability of the surface, the static contact angle was measured by the sessile drop method. Then, subsequent hydrophobic recovery was investigated by comparing UV/ozone treated polymer samples with identical samples treated using oxygen plasma. Function groups on the surface before and after UV/ozone treatment were characterized using X-ray photoelectron spectroscopy (XPS).
It was found