Modelling the Wound Healing Micro-Environment with Dynamically Adhesive Biomaterials
John Connelly,
Senior Lecturer,
Queen Mary University of London
Wound healing is a well-orchestrated, multi-stage process that is essential for tissue repair; however, the highly complex and dynamic wound environment presents challenges for controlled studies into the underlying regulatory mechanisms. To address this problem, we developed a novel in vitro model of wound healing using micro-patterned polymer brushes, and light-activated, thiol-alkyne coupling reactions. This strategy affords precise control the adhesive interactions between cells and their extracellular environment over both space and time. Specific functionalisation of micro-patterned polymer surfaces with synthetic ECM-mimetic peptides promotes cell adhesion, spreading, and migration into previously non-adhesive areas, and migration speed could be tuned by adjusting the surface ligand density. This system is also compatible with a range of cell types, including fibroblasts, simple epithelia, keratinocytes, and endothelial cells. We further demonstrate that these dynamically adhesive patterns can be used to study fundamental mechanisms of collective cell migration and gain new insights into re-epithelialisation and wound repair. On-going work in our laboratory is now focused on adapting this technology for high-throughput and high-content analysis of cell migration and extending the current platform to 3D hydrogels.
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