Photoresponsive Sulfide-based Antibacterial Composite Coatings On Titanium Implants

Titanium and titanium alloys with great biocompatible are widely used in the manufacture of medical devices to maintain normal life activities of the human body.However,due to the bacterial infection on the surface of the implant and the formation of bacterial biofilm,implant failure cases are common.Nowadays,the removal of infected implants by secondary surgery is the only viable treatment.These strategies have prolonged hospitalization periods and increased psychological burden arising from these infections.Therefore,it is urgent to develop advanced methods to rapidly and efficiently eliminate implant infection and promote bone regeneration.Nowadays,the general surface modification strategies for antimicrobial biomaterials involve enhancing the antibacterial activity of the biomaterial itself,i.e.,killing bacteria directly through antimicrobial agents in materials,such as loaded drugs,surface charge and released metallic ions(Ag⁺,Zn²⁺,Cu²⁺)or resisting bacterial adhesion through electrostatic repulsion and superhydrophobicity of surface components.These methods are characterized as"endogenous antimicrobial".However,endogenous antimicrobial strategies often require much more time to kill bacteria,which inevitably induce the formation of bacterial resistance during repeated actions.In addition to bacterial resistance to organic antibiotics,inorganic antibacterial agents,even nanosilver,can also be resisted by mutant bacteria during long-term interactions.Based on the above problems,it is necessary to construct some functional coatings on the surface of titanium and titanium alloy,which have the effect of rapid sterilization and good biocompatibility.Photothermal therapy(PTT)and photodynamic therapy(PDT)induced by light irradiation are attractive therapeutic strategies due to their unique advantages,such as nonresistance,few side effects and low systemic toxicity.Laser-induced hyperthermia based on photothermal conversion agents can destroy bacteria via various thermal effects,such as breakdown of the cell membrane or denaturation of proteins/enzymes.Laser-induced ROS has been reported to induce initial oxidative lesions to the cell wall and membrane to cause bacterial death.In this paper,the photothermal and photodynamic activities of sulfide composites are investigated,and then we prepare a biofunctional coating on the surface of titanium implants that has both near-infrared response and obvious antibacterial activity and stimulation of osteogenesis properties.The basic contents of the study include the following work:(1)Construction of photosensitive hydrogel system based on Cu S nanoparticlesThe Cu S nanoparticles were prepared by the reaction of copper chloride and sodium sulfide.After surface modification,the functionalized Cu S nanoparticles were loaded into the poly NIPAAm-co-AAm composite hydrogel.With 808 nm near-infrared(NIR)light irradiation,the materials possess excellent and controllable photothermal and photodynamic properties as well as an antibacterial efficacy of 99.80%and 99.94%against Staphylococcus aureus and Escherichia coli within 10 min,respectively.The excellent performance stems from the combined effects of hyperthermia,radical oxygen species,and released copper ions produced during NIR irradiation of Cu S NPs.In addition,the release of copper ions from the composite hydrogel samples can effectively promote the expression of angiogenesis related genes,thus rapidly promoting wound healing.(2)Construction of Mo S₂coating on titanium implant by magnetron sputtering systemA uniform Mo S₂ coating was sputtered on the surface of the titanium by a magnetron sputtering system.By electrostatic binding forces,the positively charged IR780 can be immobilized onto the negatively charged Mo S₂ film.RGDC can also be grafted onto Ti plates through a Michael addition reaction with polydopamine(PDA).The magnetron-sputtered Mo S₂ film possesses excellent photothermal properties,and IR780 can produce reactive oxygen species(ROS)under 808 nm near-infrared(NIR)light irradiation.The system successfully combines photothermal therapy and photodynamic therapy in a single platform.In addition,cell experiments further demonstrate the biocompatibility of the hybrid coating.(3)Study on the antibacterial properties and osteogenesis of Mo S₂/IR780/RGDC composite coating on titanium implantThe Mo S₂ coating constructed by the magnetron sputtering system has good adhesion to the titanium substrate.The subendothelial implant experiment demonstrates the penetration effect of near-infrared light and the high-efficiency antibacterial efficiency of the composite coating.The system can quickly eradication the biofilm formed on the surface of the implant,with the antibacterial efficiency reaching to 98.99±0.42%within 20 min.In addition,RGDC,as a natural bioactive material,can promote bone conduction effect.Compared with the pure titanium group,the composite coating has an obvious effect of promoting bone formation.According to the analysis of the Methylene blue-acid fuchsin staining,the osteogenesis rate of the sample group reached to 52.69%after four weeks bone implant.