Biointerface Topography for Enhanced Nonviral Gene Delivery

Substrate-mediated nonviral gene delivery (SMD) represents a burgeoning area of interest in the field of tissue engineering due to its potential to facilitate localized transfection while providing the scaffolding for growing cells and regenerating tissues. Surface modifications such as topographical features can also be incorporated onto the material to improve cell behaviours, including transfection. This approach holds significant promise in the context of vascular tissue engineering, which urgently requires innovative small-diameter vascular graft (SDVG) materials. Previous work has shown that topography, particularly microgrooves, can improve vascular endothelial cell (VEC) response on SDVGs. It is proposed that microRNA-145 (miR-145) delivery can improve vascular smooth muscle cell (VSMC) responses, thus providing a comprehensive platform for improved SDVG outcomes. However, the mechanisms by which topographical features enhance biomaterial-mediated gene delivery remain unclear. Moreover, topographical cues have not been used in combination with miR- 145 and their effects on VSMCs are unknown. The aim of this thesis is to address these gaps using chitosan-grafted-polyethyleneimine (CS-PEI) as a nonviral gene carrier. This work is conducted in accordance with the central hypothesis that topography will enhance CS-PEI polyplex delivery in a feature dependent and cell-type specific manner and seeks to provide insight into how topographical cues can be rationally incorporated into biomaterials for enhanced gene delivery to various cell types.