Graphene oxide coated three-dimensional printed biphasic calcium phosphate scaffold for angiogenic and osteogenic synergy in repairing critical-size bone defect

The custom-tailored medicine requires a developmental strategy that integrates excellent osteogene-sis with mechanical stability to enhance the reconstruction of the critical-size bone defect(CSBD)and the healing process in weight-bearing bone.We prepared three-dimensional(3D)printed biphasic cal-cium phosphate(BCP)scaffolds composited with nano-graphene oxide(GO).The biological effects of the GO/BCP composite scaffolds could induce the differentiation of rat bone marrow stem cells(BM-SCs)and the migration of human umbilical vein endothelial cells(HUVECs)for bone repair.The proper ratio of GO in the composite scaffold regulated the composites’surface roughness and hydrophilicity to a suitable range for the adhesion and proliferation of BMSCs and HUVECs.Besides,the GO/BCP composite scaffold increased osteogenesis and angiogenesis by activating BMP-2,RUNX-2,Smad1/4,and VEGF.The customized intramedullary nail combined with GO/BCP scaffold was applied to repair CSBD(2.0 cm in length)in a beagle femur model.This fixation strategy was confirmed by finite element analysis.In vivo,the results indicated that the custom-made internal fixation provided sufficient stability in the early stage,ensuring bone healing in a considerable mechanical environment.At 9 months postoperatively,longitudi-nal bony union and blood vessels in osteon were observed in the CSBD area with partial degradation in the 0.3%GO/BCP group.In the three-point bending test,the ultimate load of 0.3%GO/BCP group reached over 50%of the normal femur at 9 months after repair.These results showed a promising application of osteogenic GO/BCP scaffold and custom-made intramedullary nails in repairing CSBD of the beagle femur.This effective strategy could provide an option to treat the clinical CSBD in weight-bearing bones.

One-step co-doping of ZnO and Zn^(2+)in osteoinductive calcium phosphate ceramics with synergistic antibacterial activity for regenerative repair of infected bone defect

How to endow bone grafts with long-term antibacterial activity and good bone regenerative ability to achieve the regenerative repair of infected bone defects has been the focus of the clinical treatment of osteomyelitis.The present study introduced a novel one-step route to realizing the co-doping of zinc oxide(ZnO)and zinc ion(Zn^(2+))in biphasic calcium phosphate(BCP)ceramics to utilize their synergistic antibacterial.Compared with the conventional BCP ceramics(BCP-Ca),the ZnO/Zn^(2+)co-doping ones(BCP-Zn)possessed strong antibacterial ability on E.coli and S.aureus as well as stimulated the osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)effectively.The synergistic antibacterial mechanism of ZnO and Zn^(2+)was also investigated.BCP-Zn showed excellent osteoinductivity and angiogenesis at three months postoperatively in the canine intramuscular implantation model.Moreover,BCP-Zn exhibited excellent anti-infective ability and bone regenerative repair compared to BCP-Ca and control groups in the infected bone defect model of rat femur.Collectively,these findings suggest that the simultaneous introduction of ZnO/Zn^(2+)could have immense potential to expand the application of osteoinductive BCP ceramics in the regenerative repair of infected bone defects.