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

Meiling Zhu; Kunyu Zhang; Lu Feng; Sien Lin; Qi Pan; Liming Bian; Gang Li

doi:10.1016/j.bioactmat.2020.11.002

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

Bioact Mater. 2020 Nov 10;6(5):1353-1364. doi: 10.1016/j.bioactmat.2020.11.002. eCollection 2021 May.

Authors

Meiling Zhu^{1

2

3}, Kunyu Zhang⁴, Lu Feng^{1

2}, Sien Lin^{1

2

5}, Qi Pan^{1

2}, Liming Bian^{4

5

6}, Gang Li^{1

2

5}

Affiliations

¹ Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, SAR, PR China.
² Stem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, SAR, Hong Kong, PR China.
³ The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, PR China.
⁴ Department of Biomedical Engineering, The Chinese University of Hong Kong, Hong Kong, SAR, PR China.
⁵ Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, PR China.
⁶ Centre of Novel Biomaterials, The Chinese University of Hong Kong, Hong Kong, SAR, PR China.

Abstract

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.

Keywords: Mesenchymal condensation; N-cadherin mimetic peptide; Osseointegration; Titanium dioxide (TiO2); Wnt/β-catenin signaling.