Research works on the synergistic effect of surface modified bioactive molecules and bone metal implants have been highlighted.N-cadherin is regarded as a key factor in directing cell-cell interactions during the mese...Research works on the synergistic effect of surface modified bioactive molecules and bone metal implants have been highlighted.N-cadherin is regarded as a key factor in directing cell-cell interactions during the mesenchymal condensation preceding the osteogenesis in the musculoskeletal system.In this study,the N-cadherin mimetic peptide(Cad)was biofunctionalized on the titanium metal surface via the acryloyl bisphosphonate(Ac-BP).To learn the synergistic effect of N-cadherin mimetic peptide,when tethered with titanium substrates,on promoting osteogenic differentiation of the seeded human mesenchymal stem cells(hMSCs)and the osseointegration at the bone-implant interfaces.Results show that the conjugation of N-cadherin mimetic peptide with Ac-BP promoted the osteogenic gene markers expression in the hMSCs.The biofunctionalized biomaterial surfaces promote the expression of the Wnt/β-catenin downstream axis in the attached hMSCs,and then enhance the in-situ bone formation and osseointegration at the bone-implant interfaces.We conclude that this N-cadherin mimetic peptide tethered on Ti surface promote osteogenic differentiation of hMSCs and osseointegration of biomaterial implants in vitro and in vivo.These findings demonstrate the importance of the development-inspired surface bioactivation of metal implants and shed light on the possible cellular mechanisms of the enhanced osseointegration.展开更多
基金supported by grants from Hong Kong Government Research Grant Council,General Research Fund(14120118,14160917,14120118,14108720 and T13-402/17-N)National Natural Science Foundation of China(81772322)+1 种基金Health and Medical Research Fund,Hong Kong(16170951 and 17180831)Hong Kong Innovation Technology Commission Funds(PRP/050/19FX).
文摘Research works on the synergistic effect of surface modified bioactive molecules and bone metal implants have been highlighted.N-cadherin is regarded as a key factor in directing cell-cell interactions during the mesenchymal condensation preceding the osteogenesis in the musculoskeletal system.In this study,the N-cadherin mimetic peptide(Cad)was biofunctionalized on the titanium metal surface via the acryloyl bisphosphonate(Ac-BP).To learn the synergistic effect of N-cadherin mimetic peptide,when tethered with titanium substrates,on promoting osteogenic differentiation of the seeded human mesenchymal stem cells(hMSCs)and the osseointegration at the bone-implant interfaces.Results show that the conjugation of N-cadherin mimetic peptide with Ac-BP promoted the osteogenic gene markers expression in the hMSCs.The biofunctionalized biomaterial surfaces promote the expression of the Wnt/β-catenin downstream axis in the attached hMSCs,and then enhance the in-situ bone formation and osseointegration at the bone-implant interfaces.We conclude that this N-cadherin mimetic peptide tethered on Ti surface promote osteogenic differentiation of hMSCs and osseointegration of biomaterial implants in vitro and in vivo.These findings demonstrate the importance of the development-inspired surface bioactivation of metal implants and shed light on the possible cellular mechanisms of the enhanced osseointegration.