PDGF-BB/SA/Dex injectable hydrogels accelerate BMSC-mediated functional full thickness skin wound repair by promoting angiogenesis

Wound healing is a well-orchestrated dynamic and interactive process, which needs a favorable microenvironment and suitable angiogenesis. Platelet derived growth factor-BB (PDGF-BB) plays a crucial role in wound healing. However, the short half-life of PDGF-BB limits its efficacy. In the present study, we successfully synthesized an injectable hydrogel with sodium alginate (SA) and dextran (Dex) as a delivery system to simultaneously deliver PDGF-BB and bone marrow-derived mesenchymal stem cells (BMSCs) in the wound. Our work demonstrates that the PDGF-BB protein enhanced the survival, migration and endothelial cell (EC) differentiation of BMSCs in vitro. The PDGF-BB/SA/Dex hydrogels could sustainably release PDGF-BB with excellent biocompatibility in vitro and in vivo. Besides, these composite hydrogels loaded with BMSCs could accelerate wound healing by improving epithelialization and collagen deposition. In addition, the PDGF-BB/SA/Dex hydrogels promoted the EC-differentiation of transplanted BMSCs and proliferation of hair follicle stem cells in the wound. Furthermore, the expressions of angiogenesis-specific markers, PDGFR-beta, p-PI3K, p-Akt, and p-eNOS, were obviously increased in the PDGF-BB/SA/Dex/BMSCs group. In conclusion, the PDGF-BB/SA/Dex injectable hydrogels could accelerate BMSC-mediated skin wound healing by promoting angiogenesis via the activation of the PDGF-BB/PDGFR-beta-mediated PI3K/Akt/eNOS pathway, which may provide a new therapeutic strategy for stem cell therapy in wound healing.