Adipose-Derived Mesenchymal Stem Cell-Derived Exosomes Biopotentiated Extracellular Matrix Hydrogels Accelerate Diabetic Wound Healing and Skin Regeneration.

Wound healing is an urgent clinical challenge, particularly in the case of chronic wounds. Traditional approaches to wound healing have limited therapeutic efficacy due to lengthy healing times, risk of immune rejection, and susceptibility to infection. Recently, adipose-derived mesenchymal stem cell-derived exosomes (ADSC-exos) have emerged as a promising modality for tissue regeneration and wound repair. In this study, the development of a novel extracellular matrix hydrogel@exosomes (ECM@exo) is reported, which entails incorporation of ADSC-exos into an extracellular matrix hydrogel (ECM hydrogel). This solution forms a hydrogel at physiological temperature (≈37 °C) upon local injection into the wound site. ECM@exo enables sustained release of ADSC-exos from the ECM hydrogel, which maintains high local concentrations at the wound site. The ECM hydrogel displays good biocompatibility and biodegradability. The in vivo and in vitro results demonstrate that ECM@exo treatment effectively reduces inflammation and promotes angiogenesis, collagen deposition, cell proliferation, and migration, thereby accelerating the wound healing process. Overall, this innovative therapeutic approach offers a new avenue for wound healing via a biological hydrogel with controlled exosome release.