Advanced Biomedical Materials for Peripheral Nerve Regeneration: Design and Evaluation of Nerve Guidance Conduits

This thesis is in the publication format, and each chapter has been written as a standalone manuscript. The focus of my research was the development of appropriate biomaterials in the pursuit of a nerve guidance conduit (NGC) that reproducibly facilitates successful axonal regeneration across severe peripheral nerve injuries. This was the overriding rationale and there is a continuity in the research aim through a series of experimental studies. Each manuscript explores different relevant aspects of conduit design, including features such as porosity, surface topography and incorporation of biomolecules to help functionalise the NGCs.
Chapter I comprises a literature review of modern approaches to improving NGC design and their fabrication methods. Chapter II describes the manufacture and in vitro testing of microporous poly(glycerol sebacate)-methacrylate (PGS-M) NGCs, and the novel developments in emulsion templating techniques used to fabricate them. Chapter III evaluates the performance of these NGCs in conjunction with anti-scarring and anti-inflammatory agents in vivo identifying some limitations of this approach. Chapter IV describes a collaboration with Dr. Rebecca Lomax, who was another University of Sheffield-based PhD student. This work combined microporous PGS-M NGCs with electrospun aligned microfibres surface coated with glial cell line-derived neurotrophic factor (GDNF) and tested them in vivo. Chapter V comprises work that was completed during an academic placement at University College London working with Professor James Phillips. This research focused exploited emulsion electrospinning techniques to incorporate GDNF within PCL nanofibres. Finally, Chapter VI involved the fabrication of NGCs with these aligned GDNF-loaded nanofibres with a fibrin-based hydrogel. This last NGC was tested in an in vivo model of nerve injury at the University of Sheffield. Together, this body of work demonstrates a progression of ideas to examine how various novel approaches using materials combined with biological factors may be optimised for peripheral nerve regeneration.