Investigating the utility and exploring biological targets of enhanced micro-wound healing compounds in 2D and 3D skin models

Micro-wound healing is a dynamic, physiological process in which keratinocytes transition to an activated, migratory state to re-establish the epidermal barrier and resurface wounds. Although such wounds typically heal, effective intervention could offer enhanced micro-wound healing within mechanistically relevant timeframes. Whilst this is a rapidly evolving area, the successful development of enhanced micro-wound healing compounds (EMH compounds) requires systematic investigation of their utility and exploration of candidate protein targets. An important hurdle is the establishment of a 3D model with highly reproducible micro-wounds and cutting-edge approaches to monitor healing dynamics. We have established 2D and 3D human living skin equivalent (LSEs) models that enable us to perform automated high content image analysis to generate 'multidimensional drug profiles'. In this proposal we integrate our recently established 3D bioprinted models of wound healing to investigate the utility of EMH compounds and explore biological targets of enhanced micro-wound healing.