| Background and Objective:Biomedical implants have brought revolutionary changes to modern medicine,but they also increase the risk of infection.Implant-associated infection(IAI)is one of the most common complications of all clinical infections,which often leads to delayed healing,implantation failure,repeated surgery and even fatal systemic infection.At present,IAI is mainly treated by surgical physical debridement and relying on antibiotics.The problem of drug resistance caused by the use of antibiotics and the tedious clinical operation bring heavy burden to patients and bring great challenges to modern health care.In recent years,more and more studies have shown that engineering design of implant surface is an effective strategy to prevent or reduce bacterial infection,such as loading antibacterial active substances,grafting cationic polymers and modifying photodynamic functional materials.However,most of the existing surface modification methods have some problems,such as non-lasting effect,poor biocompatibility,weak tissue penetration and so on.Sonodynamic therapy(SDT)using ultrasound with good tissue penetration and controllability combined with nano-sonosensitizer has become a potential treatment for infectious diseases.In addition,nano-piezoelectric catalysts with high specific surface area and multi-functional physical and chemical properties promote the development of SDT.However,at present,the catalytic efficiency of most nano-piezoelectric catalysts is not satisfactory.In order to solve these problems,a "piezoelectric deposition" strategy for in-situ reduction of precious metals on polycrystalline BaTiO3(BTO)nanoparticles by piezoelectric induced electrons was proposed to construct BTO@M(M=Pt,Pd and Au)nanoheterostructures,which significantly improved the performance of piezoelectric catalysis by effectively separating piezoelectric charges and promoting the catalytic formation of reactive oxygen species(ROS).In order to obtain polymer implants with piezoelectric surface,we used simple casting method and piezoelectric deposition method to construct high performance nanoheterostructure BTO@Au on polymer polycaprolactone(PCL)surface,and finally formed implant surface piezoPCL with piezoelectric catalytic activity.The main contents of this paper are as follows:the optimization of nano-heterostructure of barium titanate/precious metal(BTO@M)and mechanism of piezoelectric catalysis to produce ROS.The BTO@Au nanoheterostructure was constructed on the polymer surface,and its physicochemical properties and surface domain-limited piezoelectric catalytic antibacterial mechanism were studied.Study on ultrasound-driven piezoPCL surface piezoelectric catalysis against bacterial infection and reinfection,and evaluate the biosafety of piezoPCL.Study on the extended application of surface piezoelectric catalysis against bacterial infection,and to explore the feasibility of piezoelectric surface domain-limited catalysis in the clearance of oral root canal infection through the model of human root canal infection in vitro.Materials and Methods:(1)The characterization of BTO@M nanoheterostructure.High resolution transmission electron microscopy,energy dispersive spectroscopy,X-ray diffraction,X-ray photoelectron spectroscopy and UV-visible diffuse reflectance spectroscopy were used to observe and characterize BTO@M.Their piezoelectric properties were characterized by electrochemical workstation and piezoresponse force microscopy.The redox ability of BTO@M was tested by oxygen reduction reaction(ORR)and hydrogen evolution reaction(HER).(2)Preparation and characterization of piezoPCL and its surface-confined piezoelectric catalytic antibacterial mechanism.The structure and piezoelectric properties of piezoPCL were characterized by scanning electron microscope,transmission electron microscope and piezoresponse force microscopy.The piezoelectric catalytic performance of piezoPCL was tested by ROS probe,and the main ROS species were identified.Taking S.aureus as the representative,the bactericidal performance and mechanism of piezoPCL surface-confined piezoelectric catalysis were studied by plate counting,antibacterial rate determination,scanning electron microscope,living/death staining and transcriptome sequencing.(3)The study of piezoelectric catalysis on the surface of ultrasound-driven implants against bacterial infection.The model of subcutaneous S.aureus infection and reinfection in rats was established.The ability of piezoPCL against bacterial infection in vivo was evaluated by plate count,antibacterial rate test,inflammatory factor detection,H&E staining and Gram staining.(4)The extended application of piezoelectric surface domain-limited catalysis in the clearance of oral root canal infection.The gutta-percha was modified by a method similar to piezoPCL to form a piezoelectric gutta-percha(piezoGP).The surface morphology of piezoGP was characterized by scanning electron microscope and energy dispersive spectroscopy.The isolated teeth of patients were collected to establish the model of root canal infection,and to explore the therapeutic effect of piezoGP on infected root canals under ultrasound.Results:(1)BTO@M heterostructure was constructed by piezoelectric deposition method,which significantly improved the performance of piezoelectric catalysis.Under ultrasound,BTO@M showed different redox ability.(2)The nano-heterostructure was constructed on the polymer surface,and the piezoelectric surface piezoPCL was prepared successfully.PiezoPCL has good piezoelectric catalytic performance.Under ultrasound stimulation,piezoPCL inhibits the survival of S.aureus through local oxidative stress and electron transport.(3)The piezoPCL not only has the ability of piezoelectric anti-infection and anti-reinfection,but also has good biological safety.(4)The piezoelectric gutta-percha,namely piezoGP,was successfully prepared.Under the action of ultrasound,piezoGP has an effective therapeutic effect on root canal infection caused by E.faecalis by surface-confined piezoelectric catalysis.Conclusions:In conclusion,we firstly successfully constructed the BTO@M nanoheterostructure by simple piezoelectric deposition method,which can effectively separate,migrate and utilize the piezo-generated charge at the metal-piezoelectric interface,thus significantly improving the piezoelectric catalytic performance.Then we use the BTO@M nanoheterostructure with high performance piezoelectric catalysis to modify the biomedical implant surface,and successfully construct a piezoelectric surface,namely piezoPCL.PiezoPCL can sterilize in limited area by piezoelectric catalysis under ultrasonic stimulation,so as to achieve the prevention and treatment of implant-related infection.Finally,the piezoelectric surface has a wide range of potential applications.We have successfully modified the gutta percha surface and can treat root canal infection by surface-confined piezoelectric catalysis.This study makes the piezoelectric catalytic surface based on metal/piezoelectric nanostructures as a potential implant modification strategy to combat bacterial infection in a non-invasive,antibiotic-independent and biocompatible manner. |
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