Abstract
Zirconia (ZrO2) scaffolds are considered promising candidates for bone regeneration owing to their excellent biocompatibility and mechanical strength. However, intrinsic bioinertness and the formation of microcracks during sintering remain major challenges that limit their clinical translation. Graphene oxide (GO), characterized by its abundant functional groups and outstanding mechanical properties, has emerged as a valuable material in tissue engineering applications. To address these issues, a silane-mediated dip-coating strategy was employed to deposit GO onto both two-dimensional glass substrates and three-dimensional (3D) ZrO2 scaffolds, resulting in the design and fabrication of a novel 3D porous GO-ZrO2 composite scaffold. The GO-coated glass substrates and GO-ZrO2 scaffolds were comprehensively characterized using multiple analytical techniques. The biocompatible and osteogenic abilities of human dental pulp stem cells (hDPSCs) seeded onto the scaffolds were assessed in vitro. Furthermore, the bone regeneration performance of the GO-ZrO2 scaffolds were evaluated in a rat calvarial critical-sized defect model. The results demonstrated that the GO layer was uniformly coated on the ZrO2 scaffolds through covalent bonding (C-O-Si and Si-O-Zr) which effectively bridged microcracks and inhibited their further propagation. Compared with the uncoated ZrO2 scaffolds, the GO-ZrO2 scaffolds exhibited increased compressive strength (1.27 ± 0.09 MPa) and elastic modulus (10.71 ± 1.20 MPa). The degradation rate of the GO-ZrO2 samples was minimal, with only a 0.54 % loss of their initial weight after 3 weeks, and no signs of pH reduction or obvious structural changes. Notably, the incorporation of GO, with its abundant oxygen-containing functional groups, significantly promoted cell adhesion, proliferation, and osteogenic differentiation of hDPSCs in vitro. Mineral deposition was markedly improved, as reflected in an increased calcium-to-phosphorus (Ca/P) atomic ratio (1.21 ± 0.03). Additionally, after an 8-week healing period in vivo, the GO-ZrO2 scaffolds demonstrated robust new bone formation. Collectively, these findings indicate that the GO-ZrO2 composite scaffolds represent a highly promising strategy for promoting bone regeneration.