Efficient Inhibition of Wear-Debris-Induced Osteolysis by Surface Biomimetic Engineering of Titanium Implant with a Mussel-Derived Integrin-Targeting Peptide.

Abstract

Wear-debris-induced osteolysis and subsequent aseptic loosening of the prosthesis are the main reasons for failed arthroplasty. Inhibition of wear-debris-induced osteoclastogenesis is thus a promising method to prolong the lifetime of prostheses. In this work, a mussel-derived peptide, capped with an integrin-targeting RGD tripeptide and a titanium (Ti)-affinity tetrapeptide with catechol groups at each end is biomimetically designed. The RGD peptide can interfere with integrin αv β3 to affect the cytoskeletal organization and functions of osteoclasts and subsequently inhibit osteoclast hyperactivation and osteoclastogenesis in vitro and in vivo, while the catechol groups could easily adhere to the TiO2 layer of the Ti implant via Ti-catechol coordination. This design thus enables the stable immobilization of the RGD peptide on Ti implants to inhibit osteoclast formation and reduce osteolysis in vivo, even with the existence of Ti wear particles. Further study reveals that the suppression of osteoclastogenesis and osteoclast polarization on the peptide coating is regulated by blocking the PI3K/AKT and NF-κB signal pathways. Considering the simplicity in the surface engineering, the highly biomimetic nature of the bioactive peptide, and efficient inhibition of wear-debris-caused osteolysis, this work thus presents a simple and efficient strategy to improve clinical outcome of prosthesis implantation in challenging conditions.