Cold Atmospheric Plasma-Activated In Situ Hydrogel Induces Hair Regeneration Via Immune Microenvironment Remodeling

Hair loss is a prevalent condition with limited effective treatments. Here, a cold atmospheric plasma (CAP)-activated in situ hydrogel is reported, which modulates the hair follicle immune microenvironment and promotes hair regeneration. CAP irradiation induces the gelation of a tyramine-grafted hyaluronic acid solution containing interleukin-2 (HTsol/IL2), forming a hydrogel (CAPgel/IL2) that retains CAP-induced reactive oxygen species and IL2 within its matrix. In vivo, subcutaneous injection of HTsol/IL2 into the dorsal skin of mice, followed by CAP exposure at the injection site, induces in situ formation of CAPgel/IL2. In a depilated mouse model, CAPgel/IL2 treatment results in significantly greater hair regeneration than other groups, characterized by enlarged hair follicles and a thickened hypodermis. The prolonged retention of IL2 in CAPgel/IL2 leads to an increased expansion of Treg within the hair follicle microenvironment. Additionally, CAPgel/IL2-treated mice exhibit accelerated skin pigmentation changes, indicating a transition from the telogen to the anagen phase. These findings suggest that CAPgel/IL2 enhances regulatory T cell expansion in the hair follicle microenvironment and may serve as a potential treatment for hair loss. Moreover, the CAP-activated IL2 delivery strategy, which modulates skin immune responses, may be extended to other immunologic skin disorders.