Amine‐Functionalized Chitosan/dECM Composite Promotes Cutaneous Regeneration and Hair Follicle Activation by Regulating Oxidative Stress and Inflammation

Hair loss associated with inflammatory scalp conditions is a growing clinical challenge. However, current FDA-approved treatments primarily stimulate hair growth without targeting the underlying oxidative stress or immune-related damage. In this study, we developed a topical, bioactive composite composed of amine-activated carboxymethyl chitosan (aaCMC) and hydrolyzed decellularized extracellular matrix (h-dECM), formulated using a dual supercritical fluid system to ensure solubility and enhance skin penetration. The resulting formulation exhibited antioxidant activity, immunomodulatory effects, and promoted extracellular matrix (ECM) remodeling in vitro. Specifically, the aaCMC + h-dECM composite reduced intracellular reactive oxygen species (ROS) levels and suppressed p38 phosphorylation in human dermal papilla cells, indicating the inhibition of senescence-related pathways. It also attenuated pro-inflammatory cytokine secretion in activated human peripheral blood mononuclear cells and significantly upregulated collagen and fibronectin expression in human dermal fibroblasts. In vivo, the composite accelerated epidermal repair and hair follicle regeneration in a UVB-induced scalp injury mouse model, demonstrating superior regenerative outcomes compared with minoxidil. These results suggest that aaCMC + h-dECM is a multi-functional regenerative platform capable of restoring scalp homeostasis through the combination of ROS modulation, immune regulation, and ECM support. This strategy may provide a multi-functional therapeutic alternative to conventional monotherapies for inflammatory hair loss.