USE OF A SELF-ASSEMBLING PEPTIDE HYDROGEL TO DELIVER CELLULAR THERAPY IN A NERVE DEFECT

Abstract

Autograft is the current gold standard in nerve defect reconstruction. Despite the successes of acellular allograft/nerve conduits, none compete with autograft, likely due to the absence of a transplanted glial cell population. The stromal vascular fraction (SVF) is a heterogenous cell isolate, that may improve nerve regeneration outcomes when transplanted at the site of a nerve defect. Self-Assembling Peptide (SAP) hydrogels are synthetic materials derived from short chains of biological amino acids. They are safe, injectable hydrogels whose charge and mechanical properties are easily tuned. The overarching hypothesis of this thesis is that SVF, when transplanted within an SAP hydrogel, tailored toward nerve regeneration and SVF viability, will lead to improved outcomes of nerve regeneration. In vitro modelling was used to select SAP hydrogels that support viable 3D culture of SVF, and 3D culture of DRG explants. Subsequent in vivo experimentation with a 10 mm rat sciatic nerve defect demonstrated that SVF, when delivered within a conduit, in a positively charged, 2.5kPa (G1) SAP hydrogel, significantly improved the rate of functional motor and sensory recovery compared to collagen controls and SAP without SVF. Overall, nerve regeneration through a conduit with the 2.5kPa SAP and SVF was at least as good as autograft. Using male SVF in female recipient rats, qPCR identification of Y chromosomal DNA suggested that SVF transplanted in SAP had increased longevity when compared to SVF transplanted in collagen and was likely incorporated into the regenerating nerve.

Date of Award	12 Aug 2024
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Alberto Saiani (Co Supervisor), Adam Reid (Main Supervisor) & Alessandro Faroni (Co Supervisor)