Umbilical cord mesenchymal stem cell exosomes combined with collagen sponges contribute to neovascularization and wound healing in exposed bone wounds

Unmanaged bone exposed wounds that don't receive proper treatment can potentially lead to additional complications. Human umbilical cord mesenchymal stem cell (HUC-MSC)-derived exosomes (EXO) have a significant effect in promoting wound healing. HUC-MSCs and HUC-MSC-derived EXOs were added to a CS to prepare HUC-MSC + CS and HUC-MSC EXO + CS complexes, respectively. The CS and prepared CS complexes were observed by scanning electron microscopy and applied to bone-exposed large-area skin wounds in rabbits. Then, wound tissues were collected and analyzed. Hematoxylin and eosin and Masson staining were performed to observe histopathological features in wound tissues. Immunohistochemistry and immunofluorescence were performed to observe neovascularization and neural fiber density. The expressions of growth factors (platelet-derived growth factor receptor β [PDGFR-β], vascular endothelial growth factor receptor 2 [VEGFR2], and epidermal growth factor receptor [EGFR]) in wound tissues were detected by western blotting. On healing days 3, 7, 10, 14, and 16, compared with the control group, wounds in the CS group healed well. Coverage by collagen fiber was evident, angiogenic factor CD34 expression and neural fiber density increased, along with high EGFR, PDGFR-β, and VEGFR2 levels. Compared with the CS group, the HUC-MSC + CS and HUC-MSC EXO + CS groups had a better neovascularization and wound healing. In particular, the HUC-MSC EXO + CS group showed abundant collagen. In the treatment of bone-exposed wounds, HUC-MSCs and HUC-MSC-derived EXOs loaded in CS were more efficient than CS alone, contributing to neovascularization in wounds.