Advancements in diabetic foot ulcer therapy: The role of exosomes and decellularised extracellular matrix scaffolds.

Diabetic foot ulcer (DFU) ranks among the most severe complications of diabetes mellitus. DFU mainly arises from neuropathy and peripheral arterial disease, with aggravating factors like infection and edema. These ulcers impose significant physical and financial challenges, making wound healing a crucial clinical issue. Current DFU management focuses on ensuring adequate blood flow, relieving pressure, controlling infection, and debridement. Cell therapy offers notable benefits, yet the effectiveness of traditional stem cell transplants for DFU remains contentious. In this context, exosomes are gaining recognition as a promising option in tissue engineering and regenerative medicine. Their advantages include excellent biocompatibility, precise targeting, and ability to cross biological barriers, proficient drug delivery, low toxicity, and abundant availability. Numerous studies indicate that stem cell-derived exosomes contribute to diabetic wound healing by promoting angiogenesis, collagen deposition, and reducing inflammation, among other mechanisms. This acellular approach presents significant advantages over conventional methods and is crucial in DFU management. Nonetheless, challenges such as the limited retention of exosomes at injury sites render singular treatment strategies insufficient for optimal outcomes. By integrating decellularized extracellular matrix (dECM)-based scaffolds with exosomes, enhanced transfer and retention of exosomes can be achieved, along with a sustained release. This review summarizes the role and mechanisms of exosomes from various stem cells in enhancing DFU wound healing, recent advancements in dECM scaffolds, and discusses the application of exosomes combined with dECM scaffolds in DFU therapy, along with the associated challenges.