Bio-clickable mussel-inspired peptides improve titanium-based material osseointegration synergistically with immunopolarization-regulation

ABSTRACT: Upon the osteoporotic condition, sluggish osteogenesis, excessive bone resorption, and chronic inflammation make the osseointegration of bioinert titanium (Ti) implants with surrounding bone tissues difficult, often lead to prosthesis loosening, bone collapse, and implant failure. In this study, we firstly designed clickable mussel-inspired peptides (DOPA-N3) and grafted them onto the surfaces of Ti materials through robust catechol-TiO2 coordinative interactions. Then, two dibenzylcyclooctyne (DBCO)-capped bioactive peptides RGD and BMP-2 bioactive domain (BMP-2) were clicked onto the DOPA-N3-coated Ti material surfaces via bio-orthogonal reaction. We characterized the surface morphology and biocompatibility of the Ti substrates and optimized the osteogenic capacity of Ti surfaces through adjusting the ideal ratios of BMP-2/RGD at 3:1. In vitro, the dual-functionalized Ti substrates exhibited excellent promotion on adhesion and osteogenesis of mesenchymal stem cells (MSCs), and conspicuous immunopolarization-regulation to shift macrophages to alternative (M2) phenotypes and inhibit inflammation, as well as enhancement of osseointegration and mechanical stability in osteoporotic rats. In summary, our biomimetic surface modification strategy by bio-orthogonal reaction provided a convenient and feasible method to resolve the bioinertia and clinical complications of Ti-based implants, which was conducive to the long-term success of Ti implants, especially in the osteoporotic or inflammatory conditions. Graphical abstract Mussel-inspired adhesion and bio-orthogonal reactions are combined for surface modification of Ti-based implants with RGD peptide and BMP-2 peptide. Dual-functionalized Ti-based implants can enhance osteogenesis and osseointegration through promoting BMSCs adhesion and osteodifferentiation, as well as modulate macrophage polarization in the osteoporotic rats.Image 1 Highlight • A clickable mussel-inspired peptide and two DBCO-capped bioactive peptides for facile decoration of Ti prostheses via robust catechol/TiO2 coordinative interactions and click chemical reaction.• Dual functionalized Ti-based surface can improve cell anchoring and osteogenicitity by rationally adjusting the grafting ratio of BMP-2 and RGD peptides.• Dual functionalized Ti-based surface synergistically achieve M2 shifting and efficient inflammation inhibition for osseointegration.

SUBMITTER: Sun J 

PROVIDER: S-EPMC8586442 | biostudies-literature |

REPOSITORIES: biostudies-literature