创面局部生理环境严重失衡，导致创面组织多种病理性改变，破坏正常修复过程，是慢性难愈合创面修复困难的关键原因。现有微纳米纤维基创面修复材料大多针对创面单一或部分病理性改变进行设计构建，难以满足临床需求。脂肪间充质干细胞（ASCs）来源的外泌体具有向创面递送生物活性因子“鸡尾酒”，从而全面改善创面病理微环境的潜力。但如何诱导ASCs释放针对创面修复的外泌体极具挑战。本项目拟通过研究表面微拓扑结构对ASCs释放外泌体的影响及分子机制，筛选诱导释放含高丰度促修复因子外泌体的微拓扑结构表面作为外泌体诱导平台,在此基础上构建负载含高丰度促修复因子外泌体的微纳米纤维基创面修复材料，并从分子、细胞及动物水平阐明该材料对创面修复的调控作用。本项目的实施有望获得拥有自主知识产权的高效创面修复材料，具有重要的理论和临床价值。同时，基于表面微拓扑结构的诱导平台将为制备针对其他疾病治疗的外泌体提供新技术与新思路。

Microenvironment imbalance, which leads to multiple pathological changes of the wound tissue and disturbs the normal repair process, is the key reasons for the poor healing of chronic non-healing wounds. Current micro/nano fibrous wound dressing provide limited benefits to patients with chronic non-healing wounds, due to their poor regulation on the wound microenvironment. Adipose-derived mesenchymal stem cell (ASC)-derived exosomes (ASC-Exos) can deliver a cocktail of bioactive factors to the wound sites and therefore have the potential to improve the pathological microenvironment overall. But how to induce ASCs to release exosomes with an optimal cargo profile for wound healing is a big challenge. In this project, an exosome-induction platform based on surface microtopography will be built. The optimal microtopographic structures that can induce an exosome cargo profile with elevated pro-healing factors will be identified by exploring the effects of surface microtopographies on the exosome secretory properties of ASCs and the associated mechanisms. Then, the exosomes rich in pro-healing factors will be loaded on the electrospun micro/nano fibers to construct a novel wound dressing that can improve the local microenvironment overall. Finally, the effects of the wound dressing on wound healing will be evaluated at molecular, cellular and animal level. The success of the proposed research may not only develop a novel wound dressing with our own intellectual property rights but also provide an alternative exosome-induction platform based on surface microtopography for other diseases.