Anti-aging chitosan/gelatin film crosslinked by α-Arbutin for bone regeneration by free radical scavenging to prevent osteoblast senescence.

Abstract

Osteoblasts play a critical role in maintaining bone homeostasis. Senescence causes by free radical-mediated oxidative stress may affect the viability and osteogenic differentiation potential of osteoblast during bone formation. To eliminate the impacts of senescent cells by free radical scavenging is an optimal option for bone regeneration in age-related bone disease, such as osteoporosis (OP) and periodontitis. In this study, we fabricated an antioxidant film (CG-ARB) by crosslinking chitosan (C) and gelatin (G) using α-Arbutin (ARB) as a crosslinker. The morphological, physicochemical, and radical scavenging characteristics of the films were investigated. Its antioxidative ability to prevent osteoblast senescence for restoration of osteogenic differentiation was analyzed in vitro. A Sprague- Dawley (SD) rat model with critical size calvarial defect was used to evaluate the bone regeneration and biosafety in vivo. The results demonstrated that CG-ARB formed a dense fiber membrane, allowing for the gradual and sustained release of ARB for at least 10 days. ARB exerted antioxidant effect that prevented osteoblast senescence in vitro and promote bone healing in vivo. Furthermore, CG-ARB did not cause hemolysis or organ toxicity, and was therefore, considered biosafe. These results indicated that CG-ARB film could be an ideal drug delivery system (DDS) for sustained released of ARB in bone defect repair.