Date of Award

8-17-2020

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Applied Science

First Advisor

Alexandru Biris

Second Advisor

Brian Berry

Abstract

Nerve tissue damage or failure can occur for various reasons, including infection, disease, aging, and trauma. The tissue microenvironment (extracellular matrix-ECM) plays a key role in regulating the self-renewal and recovery of damaged tissue. ECM-cell interactions govern cell migration and physiology, with biochemical and biophysical boundaries being the main factors that control ECM-cell interaction. Optimizing these boundaries for the recovering tissue will create a healthy microenvironment to support and enhance the recovery rate (1, 2). We have developed a novel, multidimensional nanocomposite system that incorporates gold nanorods (AuNRs) (aspect ratio of around 3) as an artificial ECM for cell adhesion, proliferation, and cell-substrate interaction in different cell lines. This system, built using a new and relatively simple procedure, enables easy investigation of cell-substrate interactions. By utilizing polyethylene glycol (PEG), we controlled the surface chemistry of the system allowing us to deposit the AuNRs onto the different types of substrates. The ability to modify the surface chemistry of AuNRs by changing the terminal groups of PEG opens a new route to combine a layer of AuNRs with various types of cells, such as progenitor cells, mesenchymal stem cells, and Schwann cells, which could lead to new cellular therapeutic neural devices. Furthermore, we designed a 3D model based on the active layer of the AuNR nanocomposite system to investigate the in vivo feasibility of this system to regenerate and address critical nerve injuries. A simple procedure was used to fabricate the 3D model, in the form of a nerve graft of desired dimensions. This system is built using a porous biocompatible polymer, polycaprolactone, as a support material to the AuNR layer. The in vivo results indicated that the 3D conduit has excellent handling properties and behaved very well when used in a sciatic rat nerve defect model. The histology data also show that the axons bundled inside the scaffold in the following positions: Distal Center, Proximal Center, as well as in the center on the defect. Based on these preliminary but very promising results, we can conclude that the nerve conduit approach did show robust ability towards nerve regeneration.

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