Robot-assisted in situ bioprinting of gelatin methacrylate hydrogels with stem cells induces hair follicle-inclusive skin regeneration

Large skin defects caused by accidents or disease can cause fluid loss, water and electrolyte disorders, hypoproteinemia and serious infection and remain a difficult problem in clinical practice. In situ bioprinting is a promising, recently developed technology that involves timely, customized, and morphologically adapted bioprinting of bioink into tissue defects to promote the recovery of human tissues or organs. During this process, bioink is a key factor. In this study, we synthesized a biocompatible, photosensitive hydrogel material comprising gelatin methacrylate (GelMA) for robot-assisted in situ bioprinting of skin wounds. The results showed that GelMA demonstrated good printability of that supported the proliferation of skin-derived precursors (SKPs) and maintained their properties. Furthermore, in situ bioprinting of GelMA hydrogels with epidermal stem cells (EpiSCs) and SKPs onto skin wounds showed complete wound healing and functional tissue skin regeneration. The regenerated skin contains epidermis, dermis, blood vessels, hair follicles, and sebaceous glands and resembling native skin. These results provide an effective strategy for skin repair through the combined application of GelMA hydrogels, Epi-SCs, SKPs and in situ bioprinting and its promising clinical translational potential for further applications.