Biomedical subjects

David C Martin

Publications and source records attributed to David C Martin.

16 recordsLinked to original sources

PubMed2006

Polymerization of the conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) around living neural cells.

In this paper, we describe interactions between neural cells and the conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) toward development of electrically conductive biomaterials intended for direct, functional contact with electrically active tissues such as the nervous system, heart, and skeletal muscle. We introduce a process for polymerizing PEDOT around living cells and describe a neural cell-templated conducting polymer coating for microelectrodes and a hybrid conducting polymer-live neural cell electrode. We found that neural cells could be exposed to working concentrations (0.01 m) of the EDOT monomer for as long as 72 h while maintaining 80% cell viability. PEDOT could be electrochemically deposited around neurons cultured on electrodes using 0.5-1 microA/mm(2) galvanostatic current. PEDOT polymerized on the electrode and surrounded the cells, covering cell processes. The polymerization was impeded in regions where cells were well adhered to the substrate. The cells could be removed from the PEDOT matrix to generate a neural cell-templated biomimetic conductive substrate with cell-shaped features that were cell attracting. Live cells embedded within the conductive polymer matrix remained viable for at least 120 h following polymerization. Dying cells primarily underwent apoptotic cell death. PEDOT, PEDOT+live neurons, and neuron-templated PEDOT coatings on electrodes significantly enhanced the electrical properties as compared to the bare electrode as indicated by decreased electrical impedance of 1-1.5 orders of magnitude at 0.01-1 kHz and significantly increased charge transfer capacity. PEDOT coatings showed a decrease of the phase angle of the impedance from roughly 80 degrees for the bare electrode to 5-35 degrees at frequencies >0.1 kHz. Equivalent circuit modeling indicated that PEDOT-coated electrodes were best described by R(C(RT)) circuit. We found that an RC parallel circuit must be added to the model for PEDOT+live neuron and neuron-templated PEDOT coatings.

Animals↗

PubMed2006

Thermally induced solid-state phase transition of bis(triisopropylsilylethynyl) pentacene crystals.

Bis(triisopropylsilylethynyl) pentacene (TIPS pentacene) is a functionalized pentacene derivative designed to enhance both the solution solubility and solid-state packing of pentacene. In this paper, we report our observations of a solid-state phase transition in TIPS pentacene crystals upon heating or cooling. Evidence from differential scanning calorimetry (DSC), hot-stage optical microscopy, as well as high-temperature X-ray and electron diffraction are presented. A reasonable match with experimental data is obtained with molecular modeling. Our results reveal that the transition is associated with a conformational reorganization of the TIPS side groups, accompanied by a slight decrease in the acene-to-acene spacing and a shift of the overlap between the neighboring pentacene units. The observed cracking should be avoided or minimized in TIPS pentacene-based thin film transistors to maintain their relatively high charge carrier mobility.

Calorimetry, Differential Scanning↗

PubMed2006

Triphasic nanocolloids.

Triphasic nanocolloids, that is, nanocolloids with three distinct compartments, were successfully produced by use of electrified co-jetting. Simultaneous manipulation of the three parallel liquid with laminar flows yielded a liquid droplet with three interfaces between the jetting liquids. Under a high electric potential, a single liquid jet was produced from the triple point of the droplet. Separation between the phases was maintained throughout the jetting process and resulted in triphasic nanocolloids. Poly(ethylene oxide), poly(acrylic acid), and poly(acrylamide-co-acrylic acid) solutions were used and verified to be compatible with the process. Fluorescent-labeled biomolecules were selectively incorporated in each phase of the nanocolloids, and confocal laser scanning microscopy was employed for the characterization. Scanning electron microscopy results verified that the sizes of the colloids are in the range of nanocolloids. This simple and versatile technique to fabricate multicompartment nanocolloids is expected to have great impact on drug delivery, molecular imaging, and smart displays.

Journal Article↗

PubMed2006

Imaging of crystal morphology and molecular simulations of surface energies in pentacene thin films.

We have investigated the crystal growth of the organic semiconductor pentacene by complementing molecular simulations of surface energies with experimental images of pentacene films. Pentacene thin films having variations in thickness and grain size were produced by vacuum sublimation. Large (approximately 20 microm) faceted crystals grew on top of the underlying polycrystalline thin film. The films were characterized using optical microscopy (OM), X-ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Single crystals most commonly grew in a truncated diamond shape with the largest crystal face, (001), growing parallel to the substrate. Crystal morphologies and surface energies were calculated using force field-based molecular simulations. The (001) surface was found to have the lowest energy, at 76 mJ/m(2), which was consistent with experimental observations of crystal face size. It was demonstrated that the morphology of the large faceted crystals approached the equilibrium growth shape of pentacene. From contact angle measurements, the critical surface tension of textured pentacene thin films in air was determined to be 34 mJ/m(2).

Journal Article↗

PubMed2006

Chronic neural recordings using silicon microelectrode arrays electrochemically deposited with a poly(3,4-ethylenedioxythiophene) (PEDOT) film.

Conductive polymer coatings can be used to modify traditional electrode recording sites with the intent of improving the long-term performance of cortical microelectrodes. Conductive polymers can drastically decrease recording site impedance, which in turn is hypothesized to reduce thermal noise and signal loss through shunt pathways. Moreover, conductive polymers can be seeded with agents aimed at promoting neural growth toward the recording sites or minimizing the inherent immune response. The end goal of these efforts is to generate an ideal long-term interface between the recording electrode and surrounding tissue. The goal of this study was to refine a method to electrochemically deposit surfactant-templated ordered poly(3,4-ethylenedioxythiophene) (PEDOT) films on the recording sites of standard 'Michigan' probes and to evaluate the efficacy of these modified sites in recording chronic neural activity. PEDOT-coated site performance was compared to control sites over a six-week evaluation period in terms of impedance spectroscopy, signal-to-noise ratio, number of viable unit potentials recorded and local field potential recordings. PEDOT sites were found to outperform control sites with respect to signal-to-noise ratio and number of viable unit potentials. The benefit of reduced initial impedance, however, was mitigated by the impedance contribution of typical silicon electrode encapsulation. Coating sites with PEDOT also reduced the amount of low-frequency drift evident in local field potential recordings. These findings indicate that electrode sites electrochemically deposited with PEDOT films are suitable for recording neural activity in vivo for extended periods. This study also provided a unique opportunity to monitor how neural recording characteristics develop over the six weeks following implantation.

Action Potentials↗

PubMed2006

Sustained release of dexamethasone from hydrophilic matrices using PLGA nanoparticles for neural drug delivery.

The release of the anti-inflammatory agent dexamethasone (DEX) from nanoparticles of poly(lactic-co-glycolic acid) (PLGA) embedded in alginate hydrogel (HG) matrices was investigated. DEX-loaded PLGA nanoparticles were prepared using a solvent evaporation technique and were characterized for size, drug loading, and in-vitro release. The crosslinking density of the HG was studied and correlated with drug release kinetics. The amount of DEX loaded in the nanoparticles was estimated as approximately 13 wt%. The typical particle size ranged from 400 to 600 nm. The in-vitro release of DEX from NPs entrapped in the HG showed that 90% of the drug was released over 2 weeks. The impedance of the NP-loaded HG coatings on microfabricated neural probes was measured and found to be similar to the unmodified and uncoated probes. The in-vivo impedance of chronically implanted electrodes loaded with DEX was maintained at its initial level, while that of the control electrode increased by 3 times after about 2 weeks after implantation until it stabilized at approximately 3 MOmega. This improvement in performance is presumably due to the reduced amount of glial inflammation in the immediate vicinity of the DEX-modified neural probe.

Animals↗

PubMed2006

Surface modification of neural probes with conducting polymer poly(hydroxymethylated-3,4- ethylenedioxythiophene) and its biocompatibility.

A novel conducting polymer, poly(hydroxymethylated-3,4-ethylenedioxythiophene) (PEDOT-MeOH), was electrochemically deposited onto the electrodes of micromachined neural probes. Uniformly distributed film was obtained from aqueous solution when doped with polystyrenesulfonate. The surface morphology was rough and had good cellular adhesion. Impedance spectroscopy showed that the magnitude of coated electrode was lower than that of the bare gold over a range of frequencies from 10(0)to 10(5) Hz. Since the biocompatibility of the interface between the neural probes and brain tissue plays an important role when the probes are implanted in the central nervous system for long-term application, biomolecules were incorporated into the coating. Nonapeptide CDPGYIGSR was codeposited as the counterion in the conducting films. The surface morphology of the coating was fuzzy, providing many bioactive sites for interaction with neural cells. The magnitude of impedance was as low as 53 kOmega at the biologically relevant frequency of 1 kHz. An in vitro experiment demonstrated that the neuroblastoma cells grew preferentially on the PEDOT-MeOH/CDPGYIGSR-coated electrode sites and spread beyond the electrode area.

Bridged Bicyclo Compounds, Heterocyclic↗

PubMed2005

A finite-element model of the mechanical effects of implantable microelectrodes in the cerebral cortex.

The viability of chronic neural microelectrodes for electrophysiological recording and stimulation depends on several factors, including the encapsulation of the implant by a reactive tissue response. We postulate that mechanical strains induced around the implant site may be one of the leading factors responsible for the sustained tissue response in chronic implants. The objectives of this study were to develop a finite-element model of the probe-brain tissue interface and analyze the effects of tethering forces, probe-tissue adhesion and stiffness of the probe substrate on the interfacial strains induced around the implant site. A 3D finite-element model of the probe-brain tissue microenvironment was developed and used to simulate interfacial strains created by 'micromotion' of chronically implanted microelectrodes. Three candidate substrates were considered: (a) silicon, (b) polyimide and (c) a hypothetical 'soft' material. Simulated tethering forces resulted in elevated strains both at the tip and at the sharp edges of the probe track in the tissue. The strain fields induced by a simulated silicon probe were similar to those induced by a simulated polyimide probe, albeit at higher absolute values for radial tethering forces. Simulations of poor probe-tissue adhesion resulted in elevated strains at the tip and delamination of the tissue from the probe. A tangential tethering force results in 94% reduction in the strain value at the tip of the polyimide probe track in the tissue, whereas the simulated 'soft' probe induced two orders of magnitude smaller values of strain compared to a simulated silicon probe. The model results indicate that softer substrates reduce the strain at the probe-tissue interface and thus may also reduce tissue response in chronic implants.

Animals↗

PubMed2005

Biphasic Janus particles with nanoscale anisotropy.

Advances in the field of nanotechnology have fuelled the vision of future devices spawned from tiny functional components that are able to assemble according to a master blueprint. In this concept, the controlled distribution of matter or 'patchiness' is important for creating anisotropic building blocks and introduces an extra design parameter--beyond size and shape. Although the reliable and efficient fabrication of building blocks with controllable material distributions will be of interest for many applications in research and technology, their synthesis has been addressed only in a few specialized cases. Here we show the design and synthesis of polymer-based particles with two distinct phases. The biphasic geometry of these Janus particles is induced by the simultaneous electrohydrodynamic jetting of parallel polymer solutions under the influence of an electrical field. The individual phases can be independently loaded with biomolecules or selectively modified with model ligands, as confirmed by confocal microscopy and transmission electron microscopy. The fact that the spatial distribution of matter can be controlled at such small length scales will provide access to unknown anisotropic materials. This type of nanocolloid may enable the design of multicomponent carriers for drug delivery, molecular imaging or guided self-assembly.

Anisotropy↗

PubMed2005

Ordered surfactant-templated poly(3,4-ethylenedioxythiophene) (PEDOT) conducting polymer on microfabricated neural probes.

Ordered conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) was electrochemically fabricated using a self-assembled medium of surfactant molecules as a template. The morphology and microstructure were extensively investigated by optical and electron microscopy, and results show that the coated films were composed of anisotropic domains having a characteristic size of 15-150 nm. The surfactant-templated ordered PEDOT films were electrochemically deposited on microfabricated neural probes with an electrode site area of 1,256 microm(2). The electrical properties were studied by electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). EIS showed a lowered magnitude of 35 kOmega (from an initial approximately 800 kOmega) at the biologically relevant frequency of 1 kHz. CV results show that the film has higher charge capacity and is more electrochemically stable than either nodular PEDOT or PPy. Furthermore, we have begun to probe the biological response to such a material intended to define the tissue-material interface. Results show that minute concentrations of the non-ionic surfactant are enough to kill all nearby cells in culture. It is possible however, to create surfactant-templated ordered PEDOT such that SH-SY5Y survive on the conductive polymer.

Biocompatible Materials↗

PubMed2005

Neuronal cell loss accompanies the brain tissue response to chronically implanted silicon microelectrode arrays.

Implantable silicon microelectrode array technology is a useful technique for obtaining high-density, high-spatial resolution sampling of neuronal activity within the brain and holds promise for a wide range of neuroprosthetic applications. One of the limitations of the current technology is inconsistent performance in long-term applications. Although the brain tissue response is believed to be a major cause of performance degradation, the precise mechanisms that lead to failure of recordings are unknown. We observed persistent ED1 immunoreactivity around implanted silicon microelectrode arrays implanted in adult rat cortex that was accompanied by a significant reduction in nerve fiber density and nerve cell bodies in the tissue immediately surrounding the implanted silicon microelectrode arrays. Persistent ED1 up-regulation and neuronal loss was not observed in microelectrode stab controls indicating that the phenotype did not result from the initial mechanical trauma of electrode implantation, but was associated with the foreign body response. In addition, we found that explanted electrodes were covered with ED1/MAC-1 immunoreactive cells and that the cells released MCP-1 and TNF-alpha under serum-free conditions in vitro. Our findings suggest a potential new mechanism for chronic recording failure that involves neuronal cell loss, which we speculate is caused by chronic inflammation at the microelectrode brain tissue interface.

Animals↗

PubMed2004

Conducting polymers grown in hydrogel scaffolds coated on neural prosthetic devices.

The conducting polymer polypyrrole (PPy) was electrochemically grown on hydrogel scaffolds deposited on the surface of microfabricated neural prosthetic devices. It is shown that the pyrrole monomer can be grown vertically through the hydrogel layer up to the surface without affecting the adjacent sites on the probes. The electrochemical properties of the conducting polymer-modified hydrogels were studied by impedance spectroscopy and cyclic voltammetry. It is also found that the conducting polymers could still be readily grown through the hydrogel after the microstructure is disrupted by freeze drying. Impedance measurements at the biologically important frequency of 1 kHz showed that the minimum impedance of this polymer-modified hydrogel was 7 kOmega. This is much lower than the minimum impedance of polypyrrole film ( approximately 100 kOmega).

Animals↗

PubMed2004

A randomized controlled open trial of population-based disease and case management in a Medicare Plus Choice health maintenance organization.

INTRODUCTION: The object of this study was to examine the effect of population-based disease management and case management on resource use, self-reported health status, and member satisfaction with and retention in a Medicare Plus Choice health maintenance organization (HMO). METHODS: Study design consisted of a prospective, randomized controlled open trial of 18 months' duration. Participants were 8504 Medicare beneficiaries aged 65 and older who had been continuously enrolled for at least 12 months in a network model Medicare Plus Choice HMO serving a contiguous nine-county metropolitan area. Members were care managed with an expert clinical information system and frequent telephone contact. Main outcomes included self-reported health status measured by the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), resource use measured by admission rates and bed-days per thousand per year, member satisfaction, and costs measured by paid claims. RESULTS: More favorable outcomes occurred in the intervention group for satisfaction with the health plan (P < .01) and the social function domain as measured by SF-36 (P = .04). There was no difference in member retention or mortality between groups. Use of skilled nursing home services was significantly lower in the intervention group than in the control (616 vs 747 days per thousand members per year, P = .02). This reduction, however, did not lead to lower mean total expenditures in the intervention group compared with the control (6828 dollars per member for 18 months vs 7001 dollars, P = .61). CONCLUSION: Population-based disease management and case management led to improved self-reported satisfaction and social function but not to a global net decrease in resource use or improved member retention.

Aged↗

PubMed2004

Low-voltage electron microscopy of polymer and organic molecular thin films.

We have demonstrated the capabilities of a novel low-voltage electron microscope (LVEM) for imaging polymer and organic molecular thin films. The LVEM can operate in transmission electron microscopy, scanning transmission electron microscopy, scanning electron microscopy, and electron diffraction modes. The microscope operates at a nominal accelerating voltage of 5 kV and fits on a tabletop. A detailed discussion of the electron-sample interaction processes is presented, and the mean free path for total electron scattering was calculated to be 15 nm for organic samples at 5 kV. The total end point dose for the destruction of crystallinity at 5 kV was estimated at 5 x 10(-4) and 3.5 x 10(-2) C/cm2 for polyethylene and pentacene, respectively. These values are significantly lower than those measured at voltages greater than 100 kV. A defocus series of colloidal gold particles allowed us to estimate the experimental contrast transfer function of the microscope. Images taken of several organic materials have shown high contrast for low atomic number elements and a resolution of 2.5 nm. The materials studied here include thin films of the organic semiconductor pentacene, triblock copolymer films, single-molecule dendrimers, electrospun polymer fibers and gold nanoparticles.

Electrons↗

PubMed2003

In vivo studies of polypyrrole/peptide coated neural probes.

Neural probes are micromachined multichannel electrode arrays that facilitate the functional stimulation and recording of neurons in the peripheral and central nervous system. For long-term implantations, surface modification is necessary for maintaining the stable connection between electrodes and neurons. The conductive polymer polypyrrole (PPy) and synthetic peptide DCDPGYIGSR were co-deposited on the electrode surface by electrochemical polymerization. The stability of PPy/DCDPGYIGSR coatings was tested in soaking experiments. It was found that the peptide was entrapped in the PPy film and did not diffuse away within 7 weeks of soaking in DI water. Coated probes were implanted in guinea pig brain for periods of 1, 2 and 3 weeks. Recording tests were performed and the impedance was monitored. The explanted probes and tissue were examined by immunocytochemical studies. Significantly more neurofilament positive staining was found on the coated electrode which indicated that the coatings had established strong connections with the neuronal structure in vivo. Good recordings were obtained from the coated sites that had neurons attached. First week tissue sections had no significant gliosis. In week 2, a layer of non-neuronal tissue consisting of mostly meningeal fibroblasts and ECM protein including at least fibronectin was formed around the probe tracks of both coated and uncoated probes. Astrocytes started to form a loosely organized layer by the end of the third week.

Animals↗

PubMed2002

Molecular packing and morphology of oligo(m-phenylene ethynylene) foldamers.

Understanding and controlling solid-state morphologies and molecular conformations is the key to optimizing the properties of materials. As an example for the influence of small chemical changes on solid-state structures, we studied oligo(m-phenylene ethynylene) foldamers, where the introduction of an endo-methyl group induces a transition from an extended all-transoid to a helical all-cisoid conformation. The resulting structural changes were analyzed by X-ray diffraction (XRD), polarized optical microscopy (POM), and low-dose high-resolution electron microscopy (LD-HREM) over several length scales from the molecular to the mesoscopic level. The strong tendency of the endo-methyl oligomer 1 to form stable compact helices in solution resulted in round droplets with an ordered hexagonal columnar (Col(ho)) liquid crystalline structure, where shrinkage during the crystallization resulted in the formation of a banded texture. On the other hand, the endo-hydrogen oligomer 2 exhibited a very different morphology; its extended linear shape was maintained during crystallization and resulted in an extended lamellar structure, which was determined by a compromise between crystalline packing and minimization of the surface area. Another pronounced difference between both molecular structures was the ability of the extended lamellar "crystals" to bend, whereas the helices form either straight or disordered domains. In addition, both materials exhibit strong surface effects, which extend considerably inside the droplet and induce uniform bending of the supramolecular structures.

Journal Article↗