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Engineering Bioactive, Piezoelectric Biomaterials for Peripheral Nerve Repair

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2022, PhD, University of Cincinnati, Engineering and Applied Science: Chemical Engineering.
The use of biomaterials for tissue repair applications presents immense potential for regenerative medicine. Soft tissue such as skin, muscle, and nerves share a similar overarching molecular paradigm for initiating the process of repair after injury. Namely, the interaction between individual cells and the surrounding microenvironment is a clear predictor of regenerative success. Phenotypic changes in cells such as stem cells, glial cells, or other progenitor cells are, largely, determined by changes in the deposited extracellular matrix. However, as cells often play some role (whether direct or indirect) in secreting, assembling, and modifying the connective matrix, this interaction is dynamic and reflects the litany of considerations for human induced changes to the microenvironment. While there is great variance in the repair success of individual damage, the microenvironment of cells is typically a useful target for improving regenerative outcomes. This work models the interdisciplinary reach of biomaterial design by exploring the use of numerous engineered substrates to direct the behavior of cell line models for soft tissue applications. A piezoelectric, electrospun polyvinylidene fluoride-trifluoroethylene (PVDF-TrFE) was specifically identified as a model substrate for nerve repair. With extensive materials, chemical, and electrical characterizations, it was emphatically determined that PVDF-TrFE fibrous scaffolds can be used to precisely influence the microenvironment of 3T3 Fibroblasts and RT4- D6P2T Schwann Cells to promote a prolonged regenerative phenotype. Additional modifications in scaffold fabrication produced numerous methods for functionalization with bioactive, decellularized extracellular matrix (dECM) proteins that are known to contribute significantly to repair. Current clinical solutions for nerve damage consist of nerve grafts, nerve conduits, and neurorrhaphies. While surgical repair is capable of retaining functionality in many patients, there are concerns related to donor site morbidity, incomplete axonal resection, and limited availability. Thus, after confirming the efficacy of various biomaterials for in Vitro models, a clinically feasible nerve conduit design was constructed entirely of electrospun, PVDF-TrFE scaffolds that maintained the relevant characteristics necessary for tissue repair. Further in Vivo testing will provide proof-of-concept for scaffold implementation, with the objective to use electrospun conduits for repair of severely transected nerves. This foundation introduces an alternative strategy to current nerve repair strategies with a cost-effective and relatively simplistic design structure. Further work will continue to improve on implementation parameters to ultimately produce a novel biomaterial for tissue repair, drug delivery, and therapeutic targeting.
Greg Harris, Ph.D. (Committee Member)
Aashish Priye, Ph.D. (Committee Member)
Jonathan Nickels, Ph.D. (Committee Member)
Leyla Esfandiari, Ph.D. (Committee Member)
134 p.

Recommended Citations

Citations

  • Orkwis, J. (2022). Engineering Bioactive, Piezoelectric Biomaterials for Peripheral Nerve Repair [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1649768103489552

    APA Style (7th edition)

  • Orkwis, Jacob. Engineering Bioactive, Piezoelectric Biomaterials for Peripheral Nerve Repair. 2022. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1649768103489552.

    MLA Style (8th edition)

  • Orkwis, Jacob. "Engineering Bioactive, Piezoelectric Biomaterials for Peripheral Nerve Repair." Doctoral dissertation, University of Cincinnati, 2022. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1649768103489552

    Chicago Manual of Style (17th edition)