MSC-derived exosomes injectable hyaluronic acid hydrogel for enhanced chronic wound healing

Abstract

Diabetic chronic wounds are characterized by delayed healing and disrupted immune response. Mesenchymal stem cell-derived exosomes (MSC^Exo) hold significant potential for enhancing wound healing by facilitating intercellular communication, reducing excessive inflammation, and supporting cell proliferation. However, direct application of MSC^Exo to wound sites often results in rapid diffusion and poor retention, limiting their therapeutic efficacy. In this study, we developed a hyaluronic acid (HA)-based injectable hydrogel system to deliver MSC^Exo for treating diabetic chronic wounds. This hydrogel system exhibited excellent cytocompatibility, biodegradability, and skin-like rheology properties. The porous structure of the hydrogel system allows for in situ retention of exosomes, enabling sustained therapeutic effects on the wound. In vitro studies demonstrated that the hydrogels enhanced the proliferation and migration of endothelial cells and fibroblasts. In vivo studies confirmed the hydrogel's ability to accelerate wound closure, enhance angiogenesis, and promote re-epithelialization. This MSC^Exo loaded injectable hydrogel system provides sustained therapeutic benefits and enhances tissue regeneration, presenting a promising clinical strategy for the treatment of chronic diabetic wounds.