Tissue repair and regeneration is a complex physiological process that requires multiple biological and physico-chemical cues acting together. Electrical regimes are particularly effective in controlling the cellular response of electrically sensitive tissues such as nerve, highlighting the need to develop new electroconductive/active microenvironments. This thesis describes the development of electroconductive/active micro/nano- fibrous scaffolds based on Bombyx mori silk fibroin (SF) for neural tissue engineering applications. Composites based on the incorporation of graphene oxide (GO) at controlled loadings (1 to 10% wt.) followed by in situ post-reduction into reduced GO (rGO) were first explored, but the electrical conductivity achieved was limited. On the other hand, functionalisation with poly(3,4-ethylenedioxythiophene)- polystyrene sulfonate (PEDOT-PSS) led to much higher conductance, readily tuned in terms of the coating concentration or by treating it with dimethyl sulfoxide (DMSO). Decoration of silk with intrinsically conductive recombinant reflectin, reported among the highest proton conductors in nature and involved in cephalopod brain neurogenesis, was also investigated. Experimental work was conducted to characterise the physico-chemical properties of the developed scaffolds. In vitro studies with neuroma NG108-15 cells showed that cellular viability was maintained in all scaffold groups, while metabolic activity and proliferation were greatly promoted from the early stages of the cell culture. Furthermore, these families of electroconductive/active scaffolds supported cell differentiation with neurite sprouting. Neurite outgrowth was observed after 5 days of culture, with neurite extensions up to 150-250 um. The data reported here suggests that these electroconductive/active microenvironments may be beneficial and could potentially outperform unmodified silk scaffolds. Overall, the study conducted here provides useful information about the combined use of silk and various electroconductive/active moieties that could be useful for the regeneration and repair process of peripheral nerves, and hint at the potential of using these electroconductive/active scaffolds in combination with exogenous electrical regimes to allow direct delivery of electrical signals and trigger the controlled release of therapeutics to the site of interest.
|Date of Award||1 Aug 2021|
- The University of Manchester
|Supervisor||Julie Gough (Supervisor) & Jonny Blaker (Supervisor)|
- Nerve repair; silk fibroin; fibre-spinning; electroconductivity