Hydroxybutyl Chitosan Hydrogel Promotes Ablative Fractional CO 2 Laser Wound Healing: A Prospective, Randomized, Split‐Face Trial and Animal Model Evidence

BACKGROUND: Although effective for atrophic acne scars, ablative fractional CO₂ laser (AFCL) causes unavoidable downtime and carries the potential for post-inflammatory hyperpigmentation (PIH). OBJECTIVES: To evaluate the efficacy and safety of hydroxybutyl chitosan (HBC) in wound healing and to investigate the possible molecular mechanisms of HBC. METHODS: Eighteen participants were enrolled in a split-face study, with each hemiface randomly assigned to receive either HBC or positive control therapy (PC: desonide cream, epidermal growth factor gel, and fusidic acid cream in combination) following AFCL. Clinical assessments included erythema, edema, pain, the time to decrustation, the skin barrier function, and melanin were assessed. In parallel, a mouse skin wound healing model was employed to investigate the effects of HBC. The expression of interferon regulatory factor 7 (IRF7) and cathepsin S (Ctss), as well as M1 and M2 macrophage polarization, was evaluated by immunohistochemistry and Western blot analysis of mouse skin tissues. RESULTS: Although HBC exhibited a slightly delayed onset of wound healing compared to the PC protocol, it achieved comparable outcomes by Days 7 and 28 between the groups. HBC showed more early pain but no steroid-related irritation and better moisturization. In mice, HBC demonstrated effects comparable to PC drugs, promoting macrophage M2 polarization and upregulating IRF7 and Ctss expression. CONCLUSIONS: HBC is effective and safe for promoting wound healing post AFCL. HBC upregulates IRF7 and Ctss expression and promotes macrophage M2 polarization. The expression of IRF7/CTSS may be correlated with M2 polarization of macrophages. CLINICAL TRIAL REGISTRATION NO: ChiCTR2200063765.