Polyhedral Oligomeric Silsesquioxane-Incorporated Gelatin Hydrogel Promotes Angiogenesis during Vascularized Bone Regeneration

Many approaches have been made toward the development of scaffolds with good biocompatibility and appreciable physicochemical properties to facilitate stem cell adhesion, osteogenic differentiation, and vascularization in tissue engineering. Nowadays, vascularization is a main bottleneck in tissue engineering strategies that is needed to be overcome and developed. Herein, we construct a series of polyhedral oligomeric silsesquioxane (POSS)-modified porous gelatin hydrogels with different POSS concentrations from 0 to 5 wt %, defined as X% POSS hydrogels (X = 0, 1, 2, 3, 4, 5) to support vascularized bone repair. The introduction of POSS into gelatin effectively promoted adhesive protein adsorption and integrin α5β1 expression, subsequently leading to enhanced adhesion of both rat bone marrow mesenchymal stem cells and human umbilical vein endothelial cells (HUVECs). In vitro experiments further demonstrated that POSS-containing hybrid hydrogels more effectively support the angiogenic tube and network formation in HUVECs than the 0% POSS hydrogel. Besides, POSS-containing hybrid hydrogels showed desirable performance as a sustained release system of vascular endothelial growth factor (VEGF) and bone morphogenetic protein-2 (BMP-2), and they further accelerated vascular network establishment and the formation of a new bone in defect regions. When the hydrogels were implanted into critical-sized rat calvarial defects in vivo, the VEGF/BMP-2-coupled 3% POSS group gained a higher blood vessel volume in the bone defect regions (5.49 ± 0.35 mm3) than the 3% POSS group (3.12 ± 0.20 mm3) and the 0% POSS group (1.57 ± 0.25 mm3), suggesting that the 3% POSS hydrogel with VEGF/BMP-2 would expedite vascularization. Based on these evaluations, our results indicated that the POSS-incorporated gelatin hydrogel would provide a promising bone graft scheme in potential clinical application of large bone defect repair.