Biointerface Topography for Enhanced Nonviral Gene Delivery
Loading...
Date
2023-12-11
Authors
Conner, Abigail
Journal Title
Journal ISSN
Volume Title
Publisher
University of Waterloo
Abstract
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.
Description
Keywords
mechanobiology, gene delivery, topography, biomaterial, tissue engineering, microRNA