Elimination of methicillin‑resistant Staphylococcus aureus biofilms on titanium implants via photothermally‑triggered nitric oxide and immunotherapy for enhanced osseointegration  

作　　者：Yong‑Lin Yu Jun‑Jie Wu Chuan‑Chuan Lin Xian Qin Franklin R.Tay Li Miao Bai‑Long Tao Yang Jiao 

机构地区：[1]Department of Pathology,Affiliated Hospital of Zunyi Medical University,Zunyi 563003,Guizhou,China [2]Laboratory Research Center,the First Affiliated Hospital of Chongqing Medical University,Chongqing 400016,China [3]Department of Blood Transfusion,Laboratory of Radiation Biology,the Second Affiliated Hospital,Army Military Medical University,Chongqing 400037,China [4]Department of Reproductive Endocrinology,Chongqing Health Center for Women and Children,Chongqing 401147,China [5]The Graduate School,Augusta University,Augusta,GA 30912,USA [6]Department of Stomatology,the Seventh Medical Center of PLA General Hospital,Beijing 100700,China

出　　处：《Military Medical Research》2024年第2期157-179,共23页军事医学研究（英文版）

基　　金：financially supported by the National Natural Science Foundation of China(82101069,82102537,82160411,82002278);the Natural Science Foundation of Chongqing Science and Technology Commission(CSTC2021JCYJ-MSXMX0170,CSTB2022BSXM-JCX0039);the First Affiliated Hospital of Chongqing Medical University Cultivating Fund(PYJJ2021-02);the Beijing Municipal Science&Technology Commission(Z221100007422130);the Youth Incubation Program of Medical Science and Technology of PLA(21QNPY116).

摘　　要：Background:Treatment of methicillin-resistant Staphylococcus aureus(MRSA)biofilm infections in implant placement surgery is limited by the lack of antimicrobial activity of titanium(Ti)implants.There is a need to explore more effective approaches for the treatment of MRSA biofilm infections.Methods:Herein,an interfacial functionalization strategy is proposed by the integration of mesoporous polydopamine nanoparticles(PDA),nitric oxide(NO)release donor sodium nitroprusside(SNP)and osteogenic growth peptide(OGP)onto Ti implants,denoted as [e-mail] physical and chemical properties of Ti-PDA@SNP-OGP were assessed by scanning electron microscopy,X-ray photoelectron spectroscope,water contact angle,photothermal property and NO release behavior.The synergistic antibacterial effect and elimination of the MRSA biofilms were evaluated by 2′,7′-dichlorofluorescein diacetate probe,1-N-phenylnaphthylamine assay,adenosine triphosphate intensity,O-nitrophenyl-β-D-galactopyranoside hydrolysis activity,bicinchoninic acid leakage.Fluorescence staining,assays for alkaline phosphatase activity,collagen secretion and extracellular matrix mineralization,quantitative real‑time reverse transcription‑polymerase chain reaction,and enzyme-linked immunosorbent assay(ELISA)were used to evaluate the inflammatory response and osteogenic ability in bone marrow stromal cells(MSCs),RAW264.7 cells and their co-culture system.Giemsa staining,ELISA,micro-CT,hematoxylin and eosin,Masson's trichrome and immunohistochemistry staining were used to evaluate the eradication of MRSA biofilms,inhibition of inflammatory response,and promotion of osseointegration of Ti-PDA@SNP-OGP in vivo.Results:Ti-PDA@SNP-OGP displayed a synergistic photothermal and NO-dependent antibacterial effect against MRSA following near-infrared light(NIR)irradiation,and effectively eliminated the formed MRSA biofilms by inducing reactive oxygen species(ROS)-mediated oxidative stress,destroying bacterial membrane integrity and causing leakage of intracellular compo

关 键 词：Polydopamine nanoparticles Methicillin-resistant Staphylococcus aureus Nitric oxide OSSEOINTEGRATION Osteo-immunomodulation Photothermal effect Titanium implants 

分 类 号：R783.1[医药卫生—口腔医学]