GelMA combined with sustained release of HUVECs derived exosomes for promoting cutaneous wound healing and facilitating skin regeneration.

It remains a clinical challenge for cutaneous wound healing and skin regeneration. Endothelial cells participate in the formation of blood vessels and play an important role in the whole process of wound healing. Recent studies suggested that exosomes contribute to the intercellular communication through paracrine pathways, and sustained release of exosomes from hydrogel-based materials provide a promising strategy for curing wound defects. In this study, we isolated exosomes derived from human umbilical vein endothelial cells (HUVECs) and found that HUVECs derived exosomes (HUVECs-Exos) could promote the proliferation and migration activities of keratinocytes and fibroblasts, which are two important effector cells for skin regeneration. Then we developed gelatin methacryloyl (GelMA) hydrogel as the wound dressing to incorporate HUVECs-Exos and applied it to the full-thickness cutaneous wounds. It demonstrated that GelMA scaffold could not only repair the wound defect, but also achieve sustained release of exosomes. The in vivo results showed accelerated re-epithelialization, promotion of collagen maturity and improvement of angiogenesis. Collectively, our findings suggested that HUVECs-Exos could accelerate wound healing and GelMA mediated controlled release of HUVECs-Exos might offer a new method for repairing cutaneous wound defects.