Templating Cell Alignment inside Polymer Tubes and on Hydrogel Surfaces For Peripheral and Central Nervous System Repair

Abstract

Cylindrical conduits for nerve injury have been limited by the difficulty of creating a microenvironment optimized for directed axonal regeneration. This thesis aims to address this limitation by generating a class of decellularized conduits that has both the native ECM environment for nerve repair and a mechanism to template aligned neurite extension. By patterning polymers relevant to the peripheral nervous system and the central nervous system with ZrO\(_{2}\) / SAMP, the biomaterials could be functionalized to template cell-assembled ECM and axonal alignment during nerve regeneration. Methods were developed to pattern the inside of PCLF tubes with ZrO\(_{2}\) / SAMP using a surface conforming shadow mask. Shadow masks were adhered by resistive heating along a nichrome wire. Reaction conditions for chamber vacuum deposition (CVD) of zirconium alkoxide and for SAMP functionalization were optimized to produce consistent chemical patterns. A method was developed to use SEM and EDS to rigorously analyze the consistency of the patterned tubes and screen them for biological studies. The PCLF conduits synthesized integrated key design parameters that enhance peripheral nerve regeneration: mechanical properties, cell adhesivity, biodegradability, surface topography, and biomolecule delivery. To develop a method of patterning OPF for injuries to the central nervous system, preliminary work investigated the feasibility of microcontact printing using PDMS stamps, as the hydrogel was found to be incompatible with CVD systems; these studies were assessed on PET as a proof of concept. The research presented in this thesis will inform future work to construct a SAMP pattern on OPF, enabling the hydrogel scaffold to template aligned, cell-assembled ECM for directed nerve regeneration.