Gelatin-CaO2/SAP/PLGA composite scaffold enhances the reparation of critical-sized cranial defects by promoting seed cell survival

Abstract

One of the most hindrance for bone tissue engineering to reconstruct a bone defect is that the insufficient oxygen supply, which has an extremely negative influence upon the survival of seed cells in the scaffold, especially during the initial transplantation period. Herein, we devised a controlled-oxygen-generating composite scaffold that removes this limitation. This oxygen-generating composite scaffold consists of calcium peroxide (CaO2)-releasing microparticles, hydrogel, and a poly(lactic-co-glycolic acid (PLGA) membrane. The microparticles, which are composed of gelatin and CaO2, are hydrolytically activated to generate oxygen when they make contact with water. The hydrogel, self-assembling peptide(SAP), and PLGA membrane were designed to prevent direct exposure of the gelatin-CaO2 microspheres to a large quantity of water and provide a three-dimensional environment for cell growth. The oxygen-generating composite scaffold has the capability of sustainably controlling oxygen generation for about 21 days in vitro and 28 days in vivo. The capacities of this oxygen-generating composite scaffold to improve seed cell survival and the reparation of bone defects were tested using peripheral blood-derived mesenchymal stem cells and a critical-sized cranial defect. Compared with the control groups, survival of seed cells both in vitro and in vivo was significantly improved when the cells were co-cultured or co-transplanted with the oxygen-generating microspheres. Moreover, the presence of the gelatin-CaO2 microspheres significantly improved the repair of bone defects. These results indicated that the oxygen-generating composite scaffold in this study has great potential to increase seed cell survival and enhance bone defect reconstruction.