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

微伤口愈合是一个动态的生理过程，其中角质形成细胞转变为活化的迁移状态，以重新建立表皮屏障并重新修复伤口。虽然这种伤口通常会愈合，但有效的干预可以在机械相关的时间范围内提供增强的微伤口愈合。虽然这是一个快速发展的领域，但成功开发增强的微伤口愈合化合物（EMH化合物）需要对其效用进行系统研究并探索候选蛋白质靶点。一个重要的障碍是建立一个具有高度可重复的微伤口和尖端方法的3D模型来监测愈合动态。我们已经建立了2D和3D人类活体皮肤等效物（LSE）模型，使我们能够执行自动化的高内容图像分析，以生成“多维药物配置文件”。在这项提案中，我们整合了我们最近建立的伤口愈合3D生物打印模型，以研究EMH化合物的效用，并探索增强微伤口愈合的生物靶点。

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.