Mesenchymal Stem Cell-Derived Exosomes Loaded with miR-155 Inhibitor Ameliorate Diabetic Wound Healing

Diabetic wounds are one of the debilitating complications that affectup to 20% of diabetic patients. Despite the advent of extensive therapies, the recoveryrate is unsatisfactory, and approximately, 25% of patients undergo amputation,thereby demanding alternative therapeutic strategies. On the basis of the individualtherapeutic roles of the miR-155 inhibitor and mesenchymal stem cells (MSC)-derived exosomes, we conjectured that the combination of the miR-155 inhibitor andMSC-derived exosomes would have synergy in diabetic wound healing. Herein, miR-155-inhibitor-loaded MSC-derived exosomes showed synergistic effects in keratino-cyte migration, restoration of FGF-7 levels, and anti-inflammatory action, leading toaccelerated wound healing mediated by negative regulation of miR-155, using aninvitroco-culture model andin vivomouse model of the diabetic wound. Furthermore,treatment with miR-155-inhibitor-loaded MSC-derived exosomes led to enhancedcollagen deposition, angiogenesis, and re-epithelialization in diabetic wounds. Thisstudy revealed the therapeutic potential of miR-155-inhibitor-loaded MSC-derived exosomes in diabetic wound healing and openedthe doors for encapsulating miRNAs along with antibiotics within the MSC-derived exosomes toward improved management ofchronic, nonhealing diabetic wounds