Functional Titanium Substrates Synergetic Photothermal Therapy for Enhanced Antibacterial and Osteogenic Performance via Immunity Regulation.

Abstract

Implant-associated infections (IAIs) significantly impair the integration between titanium (Ti) implants and bone tissues. Bacteria colonized on the surface of the implant can induce innate immune suppression of the host to resist clearance. Herein, an interfacial functionalization strategy is employed to introduce Fe^III TA nanoparticles (NPs) and acetyl Bletilla striata polysaccharide (acBSP) on the Ti substrate to obtain the Ti-TF-acBSP system. Under near-infrared (NIR) irradiation, the hyperthermal effect induced by Fe^III TA NPs directly killed bacteria. Meanwhile, macrophages are induced by acBSP to polarize into pro-inflammatory M1 phenotype, which enhanced the phagocytosis ability of macrophages and activated host innate immunity. Moreover, the asBSP instructed macrophages to secrete pro-osteogenic cytokine, which promoted osteogenic differentiation of MSCs. The results of the animal experiment in vivo confirmed that the Ti-TF-acBSP implant effectively eliminated bacterial infection under NIR irradiation, enhanced the expression of pro-inflammatory cytokine, and induced the production of bone-forming related factors. In a word, the functionalized Ti implant not only have a direct bactericidal effect but also regulate macrophage polarization as well as macrophage-mediated bactericidal and osteogenic effect. The strategy of combining photothermal therapy with immunoregulation will present a potential candidate for the development of novel antibacterial orthopedic devices.