Supercritical Fluid-Processed Multifunctional Hybrid Decellularized Extracellular Matrix with Chitosan Hydrogel for Improving Photoaged Dermis Microenvironment

To address the demand for reconstructive procedures in extensive subcutaneous tissue defects and significant dermis matrix loss, vascularized adipose tissue regeneration is essential for maintaining volume after material degradation. Accordingly, a double-crosslinked hydrogel that combines polyethylene glycol (PEG)-crosslinked carboxymethyl chitosan (CMC) with a hybrid decellularized extracellular matrix (dECM) is developed. The dECM, sourced from porcine adipose and cardiac tissues, processed using a supercritical fluid technique (scCO₂-EtOH) retains 1.5–5-fold more angiogenic and adipogenic cytokines than that processed using traditional methods. This hybrid dECM-based filler demonstrates excellent physical properties and injectability, with injection forces being significantly less than that for crosslinked hyaluronic acid (HA) fillers. Upon incubation at 37 °C, the storage modulus of the fillers increases substantially, eventually enhancing their moldability from additional crosslinking and the thermosensitive nature of collagen. Assessments in a UVB-induced photoaging mouse model indicate that the material maintains superior shape stability, durability, and supports vascularized tissue regeneration, reduces inflammation, and enhances VEGF expression and ECM maturation more effectively compared with that using other fillers. These promising results suggest that the material can serve as a highly effective multifunctional solution for injectable regenerative medical applications and is well-suited for potential clinical trials.