Choline phosphate-based bioactive hydrogel for sustained release of exosomes from adipose-derived stem cells to enhance diabetic wound healing.

Diabetic non-healing wounds remain a formidable clinical challenge, often leading to severe complications and high morbidity. Their impaired healing capacity is largely attributed to insufficient neovascularization, chronic inflammation, reduced collagen deposition, and a high risk of bacterial infection. Adipose-derived mesenchymal stem cell exosomes (AE) have shown promise in wound repair by promoting immunomodulation and neovascularization. However, traditional physical loading methods frequently result in exosome loss or inactivation, limiting their therapeutic efficacy. To overcome these limitations, we develop a Gelatin Methacryloyl-methacrylated choline phosphate bioactive hydrogel via free radical polymerization. This bioactive hydrogel incorporates AE through specific "choline phosphate-phosphatidylcholine" (CP-PC) conjugation, ensuring their stability and sustained release, while antibacterial metal-organic frameworks, activated by blue light and enhancing curcumin bioavailability, are physically blended into the hydrogel matrix. The bioactive hydrogel accelerates wound healing by suppressing bacterial growth and reducing inflammation during the initial phase, enhancing endothelial cell migration and tubule formation in the proliferative phase. In vitro and in vivo evaluations confirm its potent antibacterial, anti-inflammatory, and antioxidant activities, significantly promoting fibroblast proliferation and tissue regeneration.This bioactive hydrogel provides a promising strategy for infected diabetic wounds, overcoming traditional treatment limitations and enabling more effective clinical interventions.