Browsing by Subject "Nerve"
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Item Controlling neural cell behavior with electric field stimulation across a conductive substrate(2012-12) Nguyen, Hieu Trung 1980-; Schmidt, Christine E.Electrical stimulation of tissues induces cell alignment, directed migration, extended processes, differentiation, and proliferation, but the mechanisms involved remain largely unknown. To reveal effects of electric fields (EF) through the media on cell behavior, voltage (7.45 – 22 V), current density (36 – 106 mA/cm2), duration (2 – 24 hrs), and alternating currents (AC, 2 – 1000 Hz) were varied independently when exposed to cell cultures. It was determined that current density and duration are the primary attribute Schwann cells respond to when an EF is applied through the media. This implies that the number of charges moving across the cell surface may play a key role in EF-induced changes in cell behavior. Identical conditions were used to stimulate cells grown on the surface of a conductive substrate to examine if a scaffold can provide structural and EF cues. The effects of an EF through the substrate were examined by placing a protein gel on the surface during stimulation and observing the morphology of subsequent cell cultures and the physical topology of the gel. EFs were shown to create Ca2+ redistribution across gels and subtle changes in collagen I fibril banding. Stimulated gels were able to induce perpendicular Schwann cell alignment on newly seeded cultures days after initial EF exposure, and the cell response decreased when seeded at longer times, indicating the effects of EF on the matrix environment has a relaxation time. These findings were then integrated into a biodegradable, electrically conductive polypyrrole-poly-ε-caprolactone polymer developed by collaborators. Dorsal root ganglia placed in matrix gels on top of conducting polymer exhibited significantly longer axons when stimulated with DC and AC signals. The overall results demonstrate that EFs have a significant effect on the extracellular environment. The broad implication of this data grants researchers with the ability to physically and metabolically control cell behavior with EFs, including improved wound healing or reduced cancer metastasis.Item Skeletal muscle repair following Plantar nerve relocation on an extracellular matrix seeded with mesenchymal stem cells in PEGylated fibrin gel as a treatment model for volumetric muscle loss.(2014-08) Da Costa, Adriana Jocelyn; Farrar, Roger P.The toll skeletal muscle injury, resulting in significant muscle mass loss, has on the patient reaches far more than physical and emotional, as the tolls are financial as well. Approximately more than 3 billion dollars is spent on the initial medical costs and on subsequent disability benefits, following a volumetric muscle loss. Skeletal muscle has a robust capacity for self-repair; this propensity for repair is hindered when skeletal muscle loss is larger than 20% of the total mass of the muscle. Previous work in our lab, has shown functional and morphological improvements following the cellular therapy, with mesenchymal stem cells (MSC), as well as with nerve relocation to the extracellular matrix (ECM). To further observe the regenerative properties of the above treatments, a defect weighing approximately 307 ± 3.7 mg wet weight and measuring approximately 1x 1cm² was removed from the lateral gastrocnemius (LGAS) of male Sprague Dawley rats. Additionally, the medial branch of the plantar nerve was then relocated and implanted to the middle of the ECM. Seven days post injury bone-marrow derived mesenchymal stem cells were injected directly into the implant using a PEGylated Fibrin hydrogel (PEG). Following 56 days of recovery, partial functional restoration was observed in the LGAS ECM seeded with MSC and implanted with the plantar nerve. The LGAS produced 86.3 ± 5.8% of the contralateral LGAS, a value that was significantly higher than ECM implantation alone (p <.05). The implanted ECM seeded with MSC and implanted with the plantar nerve showed significant increases in blood vessel density and myofiber content (p <.05). The data suggest that a volumetric injury can be repaired by neurotization of an implanted muscle-derived ECM seeded with MSCs.