| IntroductionThe wide spread use of dental implants during recent decades has established them as a management strategy for restoring partial or full edentulism in general dental practice.As a consequence of the increased number of dental implants,biological complications in implant-supported tissuesprior to,during,or after the osseointegration process,also increased.The complications affecting peri-implant tissue are categorized as peri-implant mucositis and peri-implantitis.At present,non-surgical therapy seems rather ineffective and unpredictable.Howerer,It is still considered a pre-surgical hygiene phase for peri-implantitis.Surgical treatment may be required in some cases with severe bone resorption.Alternative approach besides antibiotics are urgently needed to overcome these issues.Recent advances in nanotechnology offered increased opportunities to address the global challenges in bacterial infection by killing germs with antibiotics free.Photodynamic therapy(PDT)is a non-invasive treatment where the light of a specific wavelength excites photosensitizers to generate reactive oxygen species(ROS)and singlet oxygen to eliminate pathogenic microorganisms.Antimicrobial photodynamic therapy(APDT)seems to be an innovative and promising approach for its potential to effectively eliminate unwanted pathogenic microorganisms(e.g.,in bacterial,fungal or parasitic infections)and its low tendency to induce drug resistance.Patients with chronic periodontitis treated with PDT that used the methylene blue photosensitizer and a diode laser.The efficacy of PDT was measured according to periodontal parameters that included bleeding on probing(BOP),probing pocket depth(PD)and clinical attachment loss(CAL).The PDT showed the most promising clinical results demonstrated the positive effects of using PDT alongside subgingival scaling for the treatment of chronic periodontitis.Research into the application of PDT in the treatment of peri-implantitis was recently conducted to assess the efficacy of PDT.The results showed that treatment of peri-implantitis with a PS resulted in significant reductions in in peri-implantitis against P.gingivalis,P.intermedia and Aggregatibacter actinomycetemcomitans compared with the original values.However,whether the principle of PDT can be applied to the prevention of peri-implantitis has not been reported.Antibacterial photothermal therapy(PTT)is regarded a safe and efficient strategy to deal with bacterial infections.In the most recent years,photothermal agents with enhanced near-infrared(NIR)light absorption exhibit a higher photothermal conversion efficiency.With a wavelength between 700-1400 nm,the light energy is converted into thermal energy by photothermal agents under the irradiation of NIR light.The generated heat can inhibit the development of multidrug resistant bacteria and also prevent the formation of biofilm structures.However,high temperature may cause irreversible damage to normal cells,which limits the antibacterial application of APTT in vivo.NIR rays boost blood circulation helping with cleaning up dead or damaged cells,including dead bacteria,as well as collagen production--as proven in many studies,red light waves stimulates the building of elastin and collagen production,both of which are essential for skin regeneration and helps in fading of scars and stretch marks.NIR can also decrease the expression of inflammatory factors reduce inflammation,and upregulate the expression of fibroblast growth factor receptor 1(FGFR1)and vascular endothelial growth factor(VEGF).Besides,Mild heat(45?)stimulation could recover bone defects and promote new bone formation with high efficacy.Also,the application of mild temperature to the drug-loaded paraffin film allowed a rapid stimulus response within a short time.And the generation of mild heat trigger drug release of locally administered drug.However,there is still a lack of photothermal materials with good biocompatibility,high photothermal conversion rate and temperature sensitivity to achieve mild heating in the body.Therefore,this study intends to fill these gaps from the following two aspects:(1)Develop a new photocatalytic preparation process to modify the surface of titanium alloy and improve their antibacterial activities and biological properties.(2)Explore new photothermal nanomaterials with stability and high photothermal conversion and study their antibacterial activities.Materials and methods(1)Visible-Light-Induced Photocatalytic and Antibacterial Activity of TiN CoatingThe selection of titanium and its alloys for orthopedic devices is determined by a combination of most favorable properties including good corrosion resistance,reliable mechanical performance,excellent biocompatibility and osteointegration ability.Nonetheless,once exposed to the external environment,implants are also exposed to microbial adhesion and biofilm formation which can lead to bacterial infections.Once the adhesion of bacteria dominates and eventually develops into a mature biofilm,it will lead to infections that are difficult to eliminate.Therefore,it is necessary to endue titanium implants with antibacterial properties to avoid infection while improving their bioactivity.In order to enhance the integrity of the soft tissue seal in transmucosal part surrounding dental implant and prevent invasion of bacteria,Titanium nitride(TiN)coating was prepared on the titanium surface via laser in-situ synthesis process through the laser alloying technology.Laser gas phase synthesis was carried out in a self-made reaction chamber with automatic gas distribution and electronic flowmeter.The power density of irradiated was optimized by controlling the laser output power and the flow rate of nitrogen(purity 99.9%).The phase composition and chemical component of the surface were investigated by X-ray diffraction(XRD),high resolution Transmission electron microscopy(HRTEM)and X-ray photoelectron spectroscopy(XPS).Surface topography and roughness were evaluated by field emission scanning electron microscopy(FE-SEM)and atomic force microscopy(AFM).To evaluate the wettability evolution,the contact angle measurements were performed depending on the sessile drop technique.The band gap was measured using UV-visible(UV-vis)diffuse reflectance spectra.Grampositive bacterial strains of S.aureus and Gram-negative strains of E.coli were used as the models to assess the antibacterial effect of the coatings under visible light by quantification of colony-forming units(CFUs),SEM analysis,and live/dead staining of the bacteria.To evaluate the biocompatibility,the proliferation rate and cell morphology were evaluated on human fibroblasts(NIH 3T3)using EdU assay and cell morphology assay.(2)Cobalt phosphide nanostructure as efficient Near-Infrared Light-Driven antibacterial agents with high stability and cytocompatibilityMild heating on peri-implant inflammation site will promote tissue healing,enhance the antibacterial ability of implants and control the release of antibiotics.In this work,we synthesized a series of cobalt phosphide nanoarchitectures with various morphologies(1D-CoP nanowires,2D-CoP nanoplates and 3D-CoP nanocubes)to achieve mild heating via a combined approach of template-free hydrothermal and subsequent phosphorization process.The effect of morphology on the physicochemical properties of the CoP nanomaterials were characterized.The texture properties of the resulted materials were characterized by XRD,HR-TEM and XPS.The morphology and structure details of asprepared CoP precursors and CoP nanomaterials were characterized by SEM.The UVVis-NIR spectra of various synthesized CoP nanomaterials was recorded in the range from 250 to 1100 nm.Photothermal performance was measured by using laser and thermal imager.The photothemal conversion efficiency and photothermal stability for 1D-CoP nanowires was also calculated.The correlation between morphologies of the Co-P NPs and their antibacterial activities were systematically investigated using CFUs,SEM images and live/dead fluorescence staining methods.Furthermore,the biocompatibility of the Co-P NPs were investigated in MC3T3-E1 murine osteoblastlike cells by LIVE/DEAD Viability/Cytotoxicity Kit and Cell Count Kit-8(CCK-8).In this work,we synthesized a series of cobalt phosphide nanoarchitectures with various morphologies(1D-CoP nanowires,2D-CoP nanoplates and 3D-CoP nanocubes)and investigated the effect of aspect ratios of these materials on their performances for antibacterial photothermal therapy for the first time.The effect of shape on the physicochemical properties of the CoP nanomaterials were characterized.The texture properties of the resulted materials were characterized by TEM,XRD and UV-Vis-NIR spectroscopy and XPS.The correlation between morphology of the CoP nanomaterials and their antibacterial activities were systematically investigated using colony counting,SEM images and live/dead fluorescence staining methods.Furthermore,the biocompatibility of the CoP nanoarchitectures were investigated in MC3T3-E1 murine osteoblast-like cells by LIVE/DEAD Viability/Cytotoxicity Kit and Cell Count Kit-8(CCK-8).Results(1)Visible-Light-Induced Photocatalytic and Antibacterial Activity of TiN CoatingTiN coating with excellent performance were produced successfully.The bare Ti surface presented longitudinal grooves and ridges caused during mechanical polishing process,whereas the TiN coating created cauliflower-like structures with pores surrounded by the surface and there were no obvious cracks and porosities.The peaks corresponding to the TiN were found for TiN coating surfaces,with the major diffraction peak at?62.1°(PDF card.No.38-1420).The roughness of TiN coating was significantly larger than that of bare Ti.The ? value of TiN coating tremendously decreased to 31.1°,representing its better hydrophilicity.The antibacterial activity against S.aureus and E.coil over different surfaces was evaluated.The cell growth of bacteria in TiN group can be effectively inhibited by over 60%under LED light.SEM images exhibited the number of S.aureus or E.coli colonies on the TiN+light group were significantly lower than that of the others.For live/dead fluorescence staining assay,TiN coating with light presented a significantly lower viable cells.For the EdU incorporation assay,the cells in TiN coating presented more red fluorescence indicating EdU labeling.The fluorescent staining results demonstrated that NIH 3T3 cells on TiN coating exhibited normal morphology and more pseudopodia.All the results indicated that TiN coating has no adverse effects on cell viability and can be considered a viable implant material for transmucosal part.(2)Cobalt phosphide nanostructure as efficient Near-Infrared Light-Driven antibacterial agents with high stability and cytocompatibilityCoP nanomaterials with different morphology(e.g.,nanowires,nanoplates and nanocubes)were successfully prepared via a combined approach of template-free hydrothermal and subsequent phosphorization process.Materials characterization showed that CoP nanomaterials with nanowires,nanoplates and nanocubes morphology were successfully synthesized.We found that all nanomaterials showed an impressive photothermal property as indicated by their NIR absorption capacity.In particular,1DCoP nanowires exhibited the optimal photothermal efficiency due to their higher aspect ratio.Under NIR light illumination,the temperature of the 1D-CoP nano wires suspension was increased by 45.4? within 20 min.In contrast,the temperatures of 2D-CoP nanoplates and 3D-CoP nanocubes were increased by 25.5 ? and 26.9 ?,respectively.All these CoP nanostructures have demonstrated to be effective antibacterial photothermal agents under NIR light irradiation.The 1D-CoP nanowires displayed pronounced photothermal properties.It was found that the survival rate of planktonic bacteria could be effectively inhibited by 99%within 30 min under NIR irradiation with the presence of 1D-CoP nano wires in suspension.In comparison,up to 60%of the bacteria could be killed when treated with 2D-CoP nanoplates and 3D-CoP nanocubes.Additionally,the CoP nanomaterials with various morphology showed excellent biocompatibility in contact with the mammalian cells even after 24 h and 48 h of incubation.This work emphasizes that the anisotropy plays an important role in governing the photothermal properties of NIR-driven materials.We could achieve precise and controllable mild heating in vivo by adjusting the morphology and concentration of CoP nanomaterials which will promote wound healing.Also cobalt phosphide nanoarchitectures may be serve as drug sustained release systems.It could be concluded that the CoP nanoarchitectures may find a great potential platform as a robust and effective sterilization for biomedical applications and drug sustained release systems.ConclusionsWe designed and synthesized two kinds of photo-based antibacterial nanomaterials named TiN coating and CoP nanomaterials to prevent and treat peri-implantitis.TiN coating has a wide UV-Vis absorption spectrum,showing good response in visible light region.The TiN coating demonstrated effective antibacterial properties on 24 h biofilm formation under visal light conditions.In addition,the TiN coating presents reusable photocatalytic potential and good biocompatibility on NIH 3T3 cells.The CoP nanomaterials show the optimum photothermal efficiency and photothermal stability.The CoP nanomaterials also displayed high antibacterial properties and favorable biocompatibility in vitro experiments.The anisotropy plays an important role in governing the photothermal properties of NIR-driven materials.We could achieve precise and controllable mild heating in vivo by adjusting the morphology and concentration of CoP nanomaterials.These two complementary strategies will overcome the deficiency antibacteria of photo-response and reduce tissue damage caused by high temperature of photothermal.All these studies will provide theoretical and practical basis for better prevention and treatment of peri-implantitis in the future.Innovative pointInnovation 1:The material synthesis method is green and reproducibleLaser processing has a small thermal influence on the substrate which will produce negligible thermal deformation on the processed workpiece.Also,laser processing has little pollution to the surrounding environment.Titanium nitride(TiN)coating was prepared on the surface of titanium by laser in-situ synthesis process through the laser alloying technology.The hydrothermal method is simple,practical and Eco-friendly.CoP nanomaterials with different morphology(e.g.,nanowires,nanoplates and nanocubes)were successfully prepared via a combined approach of template-free hydrothermal and subsequent phosphorization process.Innovation 2:The application of antimicrobial photodynamic therapy in the prevention of peri-implantitis.Beginning with photosensitive materials,TiN coating was prepared on the surface of titanium alloy.The coating can promote fibroblasts and adhesion which can improve the soft tissue healing and avoid pathogenicproliferation bacteria and their toxic products to affect soft tissue around implant.Under visible light irradiation,the TiN coating can show excellent antibacterial activity.and might achieve the purpose of preventing peri-implantitis pathogenic bacteria.It is believed that the TiN coating would find practical applications in the prevention and treatment of peri-implantitis.Innovation 3:Photothermal antibacterial therapy is applied to the treatment of periimplantitis.Beginning with photothermal materials,CoP nanomaterials with different morphologies were synthesized.By changing the morphology or concentration of CoP nanomaterials their photothermal properties and antibacterial properties were different which could achieve the purpose of mild heating.CoP nanomaterials show excellent antibacterial activity,but also avoid damage to normal tissues around implants. |
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