Construction Of PH/NIR Dual-responsive Interface Of Titanium-based Implants And Evaluation Of Antibacterial And Osteogenesis

In recent years,photothermal therapy（PTT）based on near-infrared radiation has received increasing attention in the research of antibacterial/anti-biofilm on the surface of implants,due to its remote controllability,minimally invasive,non-surgical,tissue penetration,no drug resistance and other advantages.The mesoporous polydopamine nanoparticles（MPDA）synthesized by our research group has the advantages of high photothermal conversion efficiency,abundant mesopores conducive to drug loading and promoting bone formation,which has a high antibacterial application potential in the multifunctional surface design of implants.However,killing bacteria/clearing biofilms using only PTT treatment strategies usually requires higher laser power,resulting in higher local temperatures.Excessive PTT temperatures can also cause damage to the surrounding normal cells/tissues when killing the bacteria/biofilms that accumulate on the surface of the material.In addition,due to the strong resistance of the formed biofilm,the internal heat distribution is not uniform,so it is impossible to completely eliminate biofilm infection by using PTT alone.Therefore,how to reduce the damage of PTT to the host cells and tissues around the implant and effectively kill bacteria/biofilms is still an urgent problem to be solved.It was found that the resistance of biofilms to external factors is regulated by bacterial quorum sensing（QS）system.Luteolin,as a quorum sensing inhibitor（QSI）,has the function of dispersing and inhibiting biofilm formation.Therefore,we envisage LUT in combination with PTT therapy to achieve a high antimicrobial/anti-biofilm performance within a low body injury range.Based on the above analysis,MPDA nanoparticles were prepared by template method,and LUT was loaded by the hollow mesoporous structure of MPDA.Thus,a photothermal nano-drug delivery system（MPDA-LUT）which can release QSIS was constructed.Subsequently,the chelation of Ca ions by MPDA was combined with biomineralization to construct the pH-responsive Ca P coating on the surface of MPDA,and the MPDA-LUT@Ca P nanoparticles were obtained.Finally,the surface modified titanium material（Ti-M-L@C）was prepared by anchoring MPDA-LUT@Ca P on the surface of titania by polydopamine-induced adhesion.The samples were characterized by scanning electron microscopy（SEM）,transmission electron microscopy（TEM）,X-ray photoelectron spectroscopy（XPS）,X-ray diffraction（XRD）,dynamic light scattering（DLS）,and Fourier transform infrared absorption spectrometer（FTIR）.Under the irradiation of 808 nm laser,the photothermal conversion properties of the material were characterized by thermocouple and thermal imager.The antibacterial properties and antibacterial mechanism of Ti-M-L@C with NIR treatment were evaluated by plate coating method,SEM,O-nitrophenol-β-D-galactoside（ONPG）hydrolysis method.The bioactivity and osteoinduction effect of Ti-M-L@C were evaluated by related cell experiments and methods in vitro.Subsequently,in vivo antibacterial properties and osteogenic repair properties of the implants were evaluated in the constructed infection model.It has been demonstrated that the acidic/low pH microenvironment created by bacteria and biofilm infection at the implant site can trigger the rapid degradation of the CAP coating of MPDA-LUT@Ca P nanoparticles on the surface of titanium material,thereby releasing luteolin for sterilization/removal of biofilm.At the same time,PTT treatment of bacterial infection can be realized by applying exogenous NIR to induce the photothermal effect of MPDA.More importantly,as the CAP coating degrades in the acidic infection microenvironment,a large number of Ca and phosphate ions are released,which can promote the process of osseointegration around the implant.Therefore,the construction of the pH/NIR dual-responsive interface on the surface of titanium implants proposed in this study can successfully achieve the effect of both antibacterial and bone formation,providing a new strategy for the multi-functional surface modification of implant materials.