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Here, a cold atmospheric plasma (CAP)\u2010activated in situ hydrogel is reported, which modulates the hair follicle immune microenvironment and promotes hair regeneration. CAP irradiation induces the gelation of a tyramine\u2010grafted hyaluronic acid solution containing interleukin\u20102 (HTsol\/IL2), forming a hydrogel (CAPgel\/IL2) that retains CAP\u2010induced 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\u2010treated 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\u2010activated IL2 delivery strategy, which modulates skin immune responses, may be extended to other immunologic skin disorders.<\/jats:p>","DOI":"10.1002\/advs.202511962","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T06:52:46Z","timestamp":1762757566000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Cold Atmospheric Plasma\u2010Activated In Situ Hydrogel Induces Hair Regeneration Via Immune Microenvironment Remodeling"],"prefix":"10.1002","volume":"13","author":[{"given":"Jung Suk","family":"Kim","sequence":"first","affiliation":[{"name":"College of Pharmacy and Research Institute of Pharmaceutical Sciences Seoul National University  Seoul 08826 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junho","family":"Byun","sequence":"additional","affiliation":[{"name":"Research Institute of Pharmaceutical Sciences, College 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