Supercritical CO₂-Decellularized amniotic ECM hydrogel promotes immunomodulatory skin regeneration

Acute ultraviolet B (UVB) exposure triggers rapid skin inflammation, characterized by immune cell infiltration, extracellular matrix (ECM) degradation, and tissue dysfunction. Although current therapeutic strategies such as hydrating dressings, hyaluronic acid/collagen formulations, and exogenous growth factors provide partial benefits, they are insufficient to promote comprehensive regeneration due to their limited ability to modulate the inflammatory and regenerative microenvironment of damaged skin. In this study, we present a decellularized porcine amniotic membrane (dPAM) hydrogel engineered via supercritical carbon dioxide (scCO₂)-based decellularization. This method effectively removes immunogenic cellular components while preserving ECM-associated bioactive molecules, including VEGF, PDGF, IL-10, and Decorin. Notably, the dPAM hydrogel preserved matrix-bound proteins such as Decorin, which have been associated with tissue regeneration and Wnt-related signaling involved in hair follicle biology. In vitro studies demonstrated that the dPAM hydrogel promotes angiogenesis in endothelial cells and attenuates M1-associated pro-inflammatory responses in macrophages. Moreover, it enhanced pro-regenerative and hair follicle-associated gene responses in human follicle-derived dermal papilla cells (HFDPCs), suggesting that dPAM hydrogel may influence Wnt-related regenerative signaling. In a UVB-induced skin inflammation murine model, the hydrogel exhibited dual functionality by attenuating early immune responses and promoting tissue repair. Collectively, these findings highlight the dPAM hydrogel as a bioactive ECM-based platform capable of creating a pro-regenerative microenvironment for cutaneous repair, with potential applications in photodamage-associated skin injury and broader regenerative biomaterial strategies.