Extracellular vesicles in hair regeneration
Yichuan Li, Yongchu Huang, Xin Luo, Zhiyuan Li, Ying Wang, Yinyi Feng, Dong Li, Yong ZhangAbstract
Alopecia encompasses a heterogeneous group of disorders with limited therapeutic options and unsatisfactory long-term outcomes. In recent years, extracellular vesicles (EVs) have attracted interest as cell-free bioactive carriers capable of modulating the hair follicle niche. The regenerative potential of EVs arises from the transfer of regulatory cargoes, including microRNAs, proteins, lipids, and other signaling molecules, which collectively reshape recipient-cell behavior. This narrative review provides a comprehensive, multi-source synthesis of EVs and related vesicular systems investigated for hair regeneration. It covers EVs from stem cells, skin-resident cells, body fluids, and immune cells, as well as plant-derived vesicles, artificially generated nanovesicles, EV mimetics, hybrid systems, and other emerging preparations. Most available evidence derives from studies of androgenetic alopecia and general hair-cycle models. Studies have also examined alopecia areata, chemotherapy-induced alopecia, and scarring alopecia. Preclinical studies indicate that EVs act on several key biological processes, including dermal papilla function preservation, hair follicle stem cell activation, angiogenesis promotion, oxidative injury reduction, and perifollicular inflammation regulation. Advances in EV engineering include donor-cell pretreatment, cargo optimization, and biomaterial-assisted delivery to improve retention, stability, and therapeutic efficacy. The review examines these advances alongside emerging clinical evidence and the main issues for clinical translation. Overall, EVs represent a promising therapeutic option for alopecia treatment. Combining precise cargo profiling, advanced bioengineering, and well-designed clinical studies may accelerate EV translation into practical hair regenerative medicine.