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

## TL;DR

A new hydrogel activated by cold plasma helps regrow hair by changing the immune environment in hair follicles.

## Contribution

A novel CAP-activated hydrogel that delivers IL2 and ROS to promote hair regeneration through immune modulation.

## Key findings

- CAPgel/IL2 treatment leads to significant hair regeneration in mice with enlarged hair follicles and thickened hypodermis.
- CAPgel/IL2 increases regulatory T cell expansion in the hair follicle microenvironment.
- Treatment accelerates skin pigmentation changes, indicating a transition from telogen to anagen phase.

## Abstract

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.

A cold atmospheric plasma‐activated in situ hydrogel (CAPgel/IL2) delivers reactive oxygen species and interleukin‐2 to modulate the hair follicle immune microenvironment, enhancing regulatory T‐cell expansion, dermal papilla cell proliferation, and the telogen‐to‐anagen transition for robust hair regeneration.