A temperature-sensitive chitosan hydrogels loaded with nano-zinc oxide and exosomes from human umbilical vein endothelial cells accelerates wound healing

The suboptimal therapeutic outcomes of diabetic foot ulcers (DFUs) represent a significant global challenge. In recent years, studies have indicated that novel dressings incorporating exosomes (Exos), nanomaterials, and hydrogels following debridement can synergistically promote tissue repair, which has been widely recognized as a promising emerging trend in the treatment of DFUs. In this study, a combination of zinc oxide nanoparticles (ZnO-NPs), Exos, and chitosan (CS) hydrogel (CS/ZnO-NPs@Exos) was applied to the full-thickness cutaneous defects in a diabetic rat model. This CS/ZnO-NPs@Exos hydrogel was applied to the wound site to achieve sustained and long-term release of Exos, allowing the evaluation of its therapeutic effects. This hydrogel significantly improved the wound closure rate in diabetic skin injuries and reduced oedema, erythema and inflammatory exudate at the wound site. These effects were characterized by enhanced re-epithelialization, reduced infiltration of inflammatory cells, increased collagen deposition, and enhanced angiogenesis in the wound area. This may be related to the Exos derived from human umbilical vein endothelial cells (HUVECs), which notably promote the migration and proliferation of fibroblasts. As a result, the CS/ZnO-NPs@Exos hydrogel offers a new therapeutic dressing for the management of diabetic wounds, with the potential to play a crucial role in clinical practice.