Fibroblast-derived exosomes in wound healing and regenerative medicine: mechanisms, therapeutic potential, and clinical perspectives.

Abstract

Skin wound healing is a complex biological process involving coordinated interactions among fibroblasts, immune cells, keratinocytes, endothelial cells, and extracellular matrix (ECM) components. Chronic and diabetic wounds remain significant clinical challenges due to persistent inflammation, oxidative stress, impaired angiogenesis, and defective tissue remodeling. Fibroblast-derived exosomes have recently emerged as promising cell-free therapeutic nanovesicles capable of regulating intercellular communication during tissue repair. These nanosized extracellular vesicles (EVs) carry diverse bioactive cargos, including microRNAs, proteins, lipids, and growth factors, which modulate inflammation, angiogenesis, cell proliferation, migration, and ECM remodeling. Recent studies have demonstrated that fibroblast-derived exosomes can accelerate wound closure, enhance granulation tissue formation, improve epidermal barrier restoration, and reduce oxidative stress in both normal and diabetic wound models. Beyond the intrinsic regenerative properties of these exosomes, increasing attention has focused on their integration with biomaterials, hydrogels, and scaffold-based delivery systems to achieve sustained and localized therapeutic effects. However, challenges such as cargo heterogeneity, isolation standardization, scalability, reproducibility, and biosafety evaluation continue to limit their clinical translation. This review summarizes the biological functions, regenerative mechanisms, and therapeutic applications of fibroblast-derived exosomes in wound healing while emphasizing translational challenges, biomaterial-assisted delivery strategies, and future perspectives for precision regenerative medicine.