Surface decoration of development-inspired synthetic N-cadherin motif via Ac-BP promotes osseointegration of metal implants

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.
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Highlights • N-cadherin is the key factor directing cell–cell interactions, during the mesenchymal condensation of hMSCs. • Biofunctionalization of N-cadherin promotes osseointegration of Ti screws in vivo. • N-cadherin biomimetic peptide promotes osteogenesis and bone formation through Wnt/β-catenin. • Ac-BP linker molecules would not influence the adhesion ratio and osteogenesis of hMSCs.