Exosome-Infused Scaffolding Systems in Chronic Wound Healing: Advances, Challenges, and Future Perspectives.

Chronic wounds, such as diabetic foot ulcers (DFUs), venous leg ulcers, and pressure sores, are non-healing or poorly healing wounds that present a clinical and financial burden on the healthcare system. Conventional wound care modalities, including wound dressings, negative pressure therapy, and growth factor delivery, have demonstrated limited success, especially in the case of chronic or refractory wounds. Recently, exosome-containing scaffolds have emerged as a promising strategy for regenerative medicine in chronic wound healing. Exosomes are nano-sized extracellular vesicles containing various bioactive factors that can promote regeneration through their regenerative, anti-inflammatory, angiogenic, and proliferative properties, which are involved in the processes of wound healing. In particular, hydrogels have been identified as a favorable platform for exosome delivery due to their excellent biocompatibility, tunable physicochemical properties, and ECM-mimetic nature. This review will highlight the biology of exosomes, different strategies for the incorporation of exosomes with scaffolds, and advances in scaffold fabrication strategies with a focus on electrospinning and three-dimensional bioprinting. Challenges to clinical translation, such as standardization and regulation of exosomes, and future research perspectives will also be discussed.