Endowing implants surface with enhanced vascularization and osseointegration via presenting triple-functional peptides.

Background: Titanium-based implants have demonstrated good mechanical properties and biocompatibility in clinical applications, however, their inherent low bioactivity and complex biological behaviors during the process of osseointegration have resulted in a high rate of long-term implant failure. Although the immobilization of highly bioactive peptides on the implant surface is an effective strategy to improve osseointegration, the existing mono- and bifunctional peptide-modified implant surfaces can hardly meet the needs of cell behavior regulation and tissue regeneration during the process of osseointegration, and there is an urgent need for the development of more efficient surface modification technologies. Methods: In the present study, a multifunctional peptide-modified implant material, MPN@K6, was successfully prepared by linking one end of a tripeptide system (cell adhesion peptide RGD, osteogenic growth peptide OGP, and pro-angiogenic peptide ang), which possesses a specific biological function, to hexameric lysine, and constructing the tripeptide system on the surface of metal-polyphenol coatings (MPNs) by means of non-covalent interactions between the lysine and the polyphenol, and then the MPN@K6 - RGD/OGP/ang was used as a peptide modification. RGD/OGP/ang. Results: The MPN@K6-RGD/OGP/Ang coating not only supported the early adhesion and migration, late osteogenesis and mineralization of BMSCs, but also promoted the adhesion, migration and vascularization of HUVECs. RT-qPCR results showed that the hybrid peptide up-regulated the expression of key factors in angiogenesis and osteogenesis. In vivo testing further confirmed these findings, with the functional peptide coating being 1.5 to 2 times more effective at inducing new bone formation at an early stage than the other two-peptide combinations, confirming the effectiveness and superiority of the tripeptide synergistic modification strategy. Conclusions: The results showed that the MPN@K6 - RGD/OGP/ang-modified implant exhibited significant advantages at the cellular level compared to different combinations of bifunctional peptide-coated forms. It was able to promote early cell migration and adhesion more efficiently, significantly induced osteoblast differentiation and mineralization, and enhanced the level of local vascularization. In a rat bone defect animal model, the material demonstrated more excellent bone repair effects and achieved better bone healing results, confirming the effectiveness and superiority of the tripeptide synergistic modification strategy. The translational potential of this article: The trifunctional peptide coating (MPN@K6 - RGD/OGP/Ang) constructed in this paper has a mild preparation process, is biologically safe, facilitates large-scale production, has a positive effect on bone tissue repair, and has a great potential for clinical application in orthopedic and dental implants.