Sustained-release of PDGF from PLGA microsphere embedded thermo-sensitive hydrogel promoting wound healing by inhibiting autophagy

Abstract

Growth factors (GFs) act as important active molecules for the treatment of skin wounds. However, their clinical translation is seriously restrained due to single function and short half-life. Besides, the underlying GFs-mediated wound healing mechanism remains elusive. Therefore, we aimed to develop a thermo-sensitive chitosan hydrogel embedding with poly lactic-co-glycolic acid (PLGA) microspheres which can deliver platelet-derived growth factor receptor (PDGF) for wound healing. The generated PDGF-PLGA hydrogel was systematically evaluated for its wound healing efficiency by the in vivo experiments, including biocompatibility testing, cell proliferation and migration, wound closure rate, granulation tissue formation and collagen deposition. Further, the expression levels of autophagy-related proteins were detected. The results showed that the PDGF-PLGA hydrogel exhibited excellent cell compatibility, cell proliferation and migration. The PDGF-PLGA hydrogel was superior to PDGF alone and control groups in promoting wound closure, granulation tissue formation and collagen synthesis. In addition, the autophagy levels were significantly decreased by PDGF hydrogel in wound tissue of treated mice as compared with PDGF alone and control groups. We also found that the autophagy activator rapamycin delayed PDGF hydrogel-mediated wound healing. This study provides a novel mechanism for the beneficial effects of PDGF-PLGA hydrogel on the wound repair.