Microenvironmental cue-regulated exosomes as therapeutic strategies for improving chronic wound healing

Exosomes, which are nanoscale vesicles secreted by almost all cell types via paracrine pathways, play a crucial role in intercellular communication. For nearly a decade, exosomes have been widely exploited to develop novel biologic therapeutic strategies for recalcitrant clinical problems such as chronic wounds. Due to the excellent biocompatibility and immune stability of exosomes, exosome-based therapy has shown greater potential for chronic wound healing than other biotherapies (e.g., transplantation of stem cells) and holds great promise for the clinical treatment of chronic wounds. Here, recent advances in regulating the features and biological functions of cell-derived exosomes by biochemical and biophysical cues in the cell microenvironment are systematically summarized. Subsequently, microenvironmental cue-regulated exosomes as therapeutic strategies to improve chronic wound healing by regulating the inflammatory response, promoting cell proliferation and migration, facilitating angiogenesis, and regulating extracellular matrix (ECM) remodeling are discussed, and hydrogel-based exosome delivery systems used in the treatment of chronic wounds are highlighted. Finally, ongoing challenges and future opportunities in this rapidly developing field are proposed.