Single human umbilical cord blood stem cells in decellularized porcine dermis-derived extracellular matrix hydrogel promote healing of skin wounds

• Decellularized porcine dermis (DP) exhibited a remarkable decline of approximately 90% in DNA. • Histological analysis confirmed the presence of retained ECM components in the DP. • Single UC-MSCs in the dECM hydrogel contribute to the regeneration of skin wounds. • Single UC-MSCs in the ECM hydrogel enhanced collagen and angiogenesis, aiding skin regeneration. This study aimed to investigate the effectiveness of a porcine decellularized dermis-derived extracellular matrix (dECM) hydrogel combined with single UC-MSCs and spheroids in promoting skin wound healing. Compared to native tissue, decellularized porcine dermis (DP) exhibited a remarkable decline of approximately 90 % in DNA content relative to the native tissue, as confirmed by the lack of nuclear staining observed through 4′,6-diamidino-2-phenylindole (DAPI) staining. Furthermore, histological analysis confirmed the presence of retained ECM components in the DP, and ECM components were quantified. Optimal concentrations of the dECM hydrogel (2, 4, and 6 mg/mL) for UC-MSCs cultivation were determined, and it was observed that a concentration of 2 mg/mL promoted better proliferation of UC-MSCs. The microstructure and mechanical strength of different dECM hydrogel concentrations were analyzed using scanning electron microscope (SEM) and rheometer. Both single UC-MSCs and spheroids in a 2 mg/mL ECM hydrogel were transplanted into mouse skin wound model to assess their effectiveness in promoting skin regeneration. It was confirmed that collagen and angiogenesis involved in skin regeneration were significantly (p < 0.05) increased in the ECM hydrogel with single UC-MSCs group, compared to spheroids MSCs. Therefore, these findings propose a promising therapeutic strategy for skin wound regeneration and recovery.