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dc.contributor.authorMukhatyar, Viveken_US
dc.date.accessioned2013-01-17T22:05:21Z
dc.date.available2013-01-17T22:05:21Z
dc.date.issued2011-11-11en_US
dc.identifier.urihttp://hdl.handle.net/1853/45933
dc.description.abstractSevere traumatic injuries and surgical procedures like tumor resection often create peripheral nerve gaps, accounting for over 250,000 injuries in the US annually. The clinical "gold standard" for bridging peripheral nerve gaps is autografts, with which 40-50% of patients regain useful function. However, issues including their limited availability and collateral damage at the donor site limit the effectiveness and use of autografts. Therefore, it is critical to develop alternative bioengineered approaches that match or exceed autograft performance. With the use of guidance channels, the endogenous regeneration process spontaneously occurs when successful bridging of short gaps (< 10mm) occurs, but fails to occur in the bridging of longer gaps (≥15mm). Several bioengineered strategies are currently being explored to bridge these critical size nerve gaps. Other labs and ours have shown how filler materials that provide topographical cues within the nerve guides are able to enhance nerve growth and bridge critical length gaps in rats. However, the mechanism by which intra-luminal fillers enhance nerve regeneration has not been explored. The main goal of this dissertation was to explore the interplay between intra-luminal scaffolds and orchestrated events of provisional fibrin matrix formation, glial cell infiltration, ECM deposition and remodeling, and axonal infiltration - a sequence we term the 'regenerative' sequence. We hypothesized that the mechanism by which thin films with topographical cues enhance regeneration is by serving as physical 'organizing templates' for Schwann cell infiltration, Schwann cell orientation, extra-cellular matrix deposition/organization and axon infiltration. We demonstrate that aligned topographical cues mediate their effects to the neuronal cells through optimizing fibronectin adsorption in vitro. We also demonstrate that aligned electrospun thin films are able to enhance bridging of a critical length nerve gap in vivo by stabilizing the provisional matrix, creating a pro-inflammatory environment and influencing the maturation of the regenerating cable leading to faster functional recovery compared to smooth films and random fibers. This research will advance our understanding of the mechanisms of peripheral nerve regeneration, and help develops technologies that are likely to improve clinical outcomes after peripheral nerve injury.en_US
dc.publisherGeorgia Institute of Technologyen_US
dc.subjectBiomaterialsen_US
dc.subjectNeural tissue engineeringen_US
dc.subjectTopographyen_US
dc.subjectRegenerative medicineen_US
dc.subject.lcshAutotransplantation
dc.subject.lcshAutografts
dc.subject.lcshTissue engineering
dc.subject.lcshNervous system Regeneration
dc.titleUnderstanding the role topographical features play in stimulating the endogenous peripheral nerve regeneration across critically sized nerve gapsen_US
dc.typeDissertationen_US
dc.description.degreePhDen_US
dc.contributor.departmentBiomedical Engineeringen_US
dc.description.advisorCommittee Chair: Ravi Bellamkonda; Committee Member: Art English; Committee Member: Philip Santangelo; Committee Member: Robert Guldberg; Committee Member: Tom Barkeren_US


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