“Dual-functional” strontium titanate nanotubes designed based on fusion peptides simultaneously enhancing anti-infection and osseointegration

Abstract

Currently, there is an increasing clinical demand for implants that effectively resist bacterial infections while promoting osseointegration. In this study, the fusion peptide technology was used to linearly fuse the antimicrobial peptide (AMP, HHC36) and the bone-promoting peptide (RGD), so that the titanium (Ti)-based implant modified by the polypeptide had the dual function of “antibacterial-promoting bone”. Firstly, self-organized vertically-oriented strontium-doped titanium dioxide nanotubes (STN) were manufactured by anodizing and hydrothermal synthesis methods. Secondly, the fusion peptide (HHC36-RGD) was loaded into the tubular structure by a simple vacuum-assisted physical adsorption method. Finally, STN loaded with HHC36-RGD (H-R-STN) was obtained. The characterization results demonstrated that the surface of the H-R-STN had a roughness and hydrophilicity that promoted cell adhesion. Additionally, electrochemical tests showed that H-R-STN coating can reduce the corrosion rate of pure Ti. The fusion peptide and Sr2+ in H-R-STN were released in the initial fast and subsequent slow kinetic model. Expected, H-R-STN can kill more than 99% of clinically common pathogenic bacteria (Staphylococcus aureus and Escherichia coli), and significantly inhibit the formation of bacterial biofilms. Simultaneously, under the synergistic effect of RGD in the fusion peptide and strontium in STN, H-R-STN markedly promoted the adhesion and proliferation of mouse osteoblasts, and significantly promoted osteogenic markers (alkaline phosphatase, runt-related transcription, collagen, mineralization) expression. In summary, the bifunctional titanium-based implant constructed by H-R-STN in this article can effectively prevent bacterial infections and promote early osseointegration. The main advantage of the titanium surface treatment method of the study was that its simplicity, low cost, especially its versatility made it a promising anti-infective bone repair material.