A dopamine-methacrylated hyaluronic acid hydrogel as an effective carrier for stem cells in skin regeneration therapy.

Adipose-derived stem cells (ADSCs) show potential in skin regeneration research. A previous study reported the failure of full-thickness skin self-repair in an injury area exceeding 4 cm in diameter. Stem cell therapies have shown promise in accelerating skin regeneration; however, the low survival rate of transplanted cells due to the lack of protection during and after transplantation leads to low efficacy. Hence, effective biomaterials for the delivery and retention of ADSCs are urgently needed for skin regeneration purposes. Here, we covalently crosslinked hyaluronic acid with methacrylic anhydride and then covalently crosslinked the product with dopamine to engineer dopamine-methacrylated hyaluronic acid (DA-MeHA). Our experiments suggested that the DA-MeHA hydrogel firmly adhered to the skin wound defect and promoted cell proliferation in vitro and skin defect regeneration in vivo. Mechanistic analyses revealed that the beneficial effect of the DA-MeHA hydrogel combined with ADSCs on skin defect repair may be closely related to the Notch signaling pathway. The ADSCs from the DA-MeHA hydrogel secrete high levels of growth factors and are thus highly efficacious for promoting skin wound healing. This DA-MeHA hydrogel may be used as an effective potential carrier for stem cells as it enhances the efficacy of ADSCs in skin regeneration.