PNIPAM hydrogel loaded with Dicliptera chinensis polysaccharides-treated ADSC-derived exosomes promotes angiogenesis to accelerate skin wound healing.

Promotion of angiogenesis is a key aspect in accelerating wound healing. Therefore, exosomal therapy is a promising method for wound healing. Dicliptera chinensis polysaccharides (DCPs) have the potential to promote angiogenesis in tissues, and a hydrogel loaded with exosomes is an ideal delivery carrier. This study demonstrates the promising biological effects of PNIPAM hydrogel-loaded ADSC-Exos pretreated with DCP in promoting skin wound healing. Exosomes secreted by adipose-derived stem cells (ADSCs) following DCP stimulation were collected and designated as DExos. In vitro experiments verified the ability of DExos to promote angiogenesis using the cell scratch technique, the angiogenesis assay, RT-qPCR, and Western Blotting using human umbilical vein endothelial cells (HUVECs) as a cell model. In vivo, a full skin defect was created on the backs of rats, and PNIPAM hydrogel loaded with DExos were injected into the defect. Wound healing was assessed morphologically and histologically. DExos promoted the cell migration rate and vasculogenic capacity of HUVECs and increased the cellular expression levels of CD31, FGF2, and VEGF-A. DExos-based poly (N-isopropylacrylamide) hydrogels (PNIPAM@DExos) enabled improved local retention and prolonged presence of DExos at the wound site, thereby promoting skin wound healing. Pretreatment of ADSCs with DCPs improves the vasculogenic capacity of exosomes, and PNIPAM@DExos promotes skin wound healing by slowly releasing DExos.