Designing Biomaterials Mimicking Regenerative Extracellular Matrix Cues of the Nervous System

Evans, Elisabeth

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Year:: 2019
Contributor:: Evans, Elisabeth (creator); Hoffman-Kim, Diane (Advisor); Jaworski, Alexander (Reader); Darling, Eric (Reader); Mathiowitz, Edith (Reader); Reichner, Jonathan (Reader); Brown University. Biology and Medicine: Artificial Organs, Biomaterials, and Cell Technology (sponsor)
Genre:: theses
Subject:: Biomedical materials; Extracellular matrix; Nerves, Peripheral
Extent:: , None p.
DOI: https://doi.org/10.26300/py1w-9843

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Abstract:: The work in this dissertation develops two different biomaterial approaches towards advancing our understanding of how neural cell behavior, specifically migration and proliferation, can respond to extracellular matrix mimetic cues. As several neural pathologies involve substantial cell population losses that are most often permanent, the potential to repopulate injured or lesioned neural tissue with a biomaterial intervention may ultimately lead towards therapies, which could mitigate functional losses. With each approach, an extracellular matrix cue was recapitulated from a native physiologic niche and presented to a specific target population of cells, each which are central to discrete regenerative processes: Schwann cells in the peripheral nervous system and adult neural stem cells that reside in multiple neurogenic niches of the central nervous system. By generating substrates inspired by physiologic stiffness gradients that are present in post-injury peripheral nerve tissue, we found that Schwann cell migration can be guided by stiffness gradients in vitro. We also found that Schwann cell morphology was influenced by stiffness gradients; Schwann cells cultured on gradient substrates displayed features characteristic of the pro-regenerative Schwann cell phenotype found in vivo. Separately in the second study, we characterized extracellular matrix enriched biomaterials, which were generated through a process of culturing and subsequently decellularizing engineered neural tissues. Comparatively, from a fabrication perspective, our matrix yield from engineered neural tissues was significantly greater than matrix yields from native neural tissues, while still preserving various biomimetic biochemical and ultrastructural matrix features. Additionally, the soluble form of the decellularized matrix derived from engineered neural tissues was able to modulate adult neural stem cell proliferation to a similar extent of a soluble form derived from native brain tissues. Overall, this study provided insight into the feasibility of using engineered tissues as equivalent and effective source tissues in lieu of native brain tissues for the development of matrix-based neuroregenerative biomaterials.
Notes:: Thesis (Ph. D.)--Brown University, 2019

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Evans, Elisabeth, "Designing Biomaterials Mimicking Regenerative Extracellular Matrix Cues of the Nervous System" (2019). Artificial Organs, Biomaterials, and Cell Technology Theses and Dissertations. Brown Digital Repository. Brown University Library. https://doi.org/10.26300/py1w-9843

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Artificial Organs, Biomaterials, and Cell Technology Theses and Dissertations

Theses and Dissertations for the Artificial Organs, Biomaterials, and Cell Technology department.
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