Biocompatible reduced graphene oxide stimulated BMSCs induce acceleration of bone remodeling and orthodontic tooth movement through promotion on osteoclastogenesis and angiogenesis

We has synthesized the biocompatible gelatin reduced graphene oxide (GOG) in previous research, and in this study we would further evaluate its effects on bone remodeling in the aspects of osteoclastogenesis and angiogenesis so as to verify its impact on accelerating orthodontic tooth movement. The mouse orthodontic tooth movement (OTM) model tests in vivo showed that the tooth movement was accelerated in the GOG local injection group with more osteoclastic bone resorption and neovascularization compared with the PBS injection group. The analysis on the degradation of GOG in bone marrow stromal stem cells (BMSCs) illustrated its good biocompatibility in vitro and the accumulation of GOG in spleen after local injection of GOG around the teeth in OTM model in vivo also didn't influence the survival and life of animals. The co-culture of BMSCs with hematopoietic stem cells (HSCs) or human umbilical vein endothelial cells (HUVECs) in transwell chamber systems were constructed to test the effects of GOG stimulated BMSCs on osteoclastogenesis and angiogenesis in vitro. With the GOG stimulated BMSCs co-culture in upper chamber of transwell, the HSCs in lower chamber manifested the enhanced osteoclastogenesis. Meanwhile, the co-culture of GOG stimulated BMSCs with HUVECs showed a promotive effect on the angiogenic ability of HUVECs. The mechanism analysis on the biofunctions of the GOG stimulated BMSCs illustrated the important regulatory effects of PERK pathway on osteoclastogenesis and angiogenesis. All the results showed the biosecurity of GOG and the biological functions of GOG stimulated BMSCs in accelerating bone remodeling and tooth movement.