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

作者全名："Yu, Yong-Lin; Wu, Jun-Jie; Lin, Chuan-Chuan; Qin, Xian; Tay, Franklin R.; Miao, Li; Tao, Bai-Long; Jiao, Yang"

作者地址："[Yu, Yong-Lin] Zunyi Med Univ, Dept Pathol, Affiliated Hosp, Zunyi 563003, Guizhou, Peoples R China; [Wu, Jun-Jie; Tao, Bai-Long] Chongqing Med Univ, Lab Res Ctr, Affiliated Hosp 1, Chongqing 400016, Peoples R China; [Lin, Chuan-Chuan] Army Mil Med Univ, Affiliated Hosp 2, Dept Blood Transfus, Lab Radiat Biol, Chongqing 400037, Peoples R China; [Qin, Xian] Chongqing Hlth Ctr Women & Children, Dept Reprod Endocrinol, Chongqing 401147, Peoples R China; [Tay, Franklin R.] Augusta Univ, Grad Sch, Augusta, GA 30912 USA; [Miao, Li; Jiao, Yang] Peoples Liberat Army Gen Hosp, Dept Stomatol, Med Ctr 7, Beijing 100700, Peoples R China"

通信作者："Yu, YL (通讯作者)，Zunyi Med Univ, Dept Pathol, Affiliated Hosp, Zunyi 563003, Guizhou, Peoples R China.; Tao, BL (通讯作者)，Chongqing Med Univ, Lab Res Ctr, Affiliated Hosp 1, Chongqing 400016, Peoples R China.; Miao, L; Jiao, Y (通讯作者)，Peoples Liberat Army Gen Hosp, Dept Stomatol, Med Ctr 7, Beijing 100700, Peoples R China."

来源：MILITARY MEDICAL RESEARCH

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000980539400001

JCR分区：Q1

影响因子：21.1

年份：2023

卷号：10

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Polydopamine nanoparticles; Methicillin-resistant Staphylococcus aureus; Nitric oxide; Osseointegration; Osteo-immunomodulation; Photothermal effect; Titanium implants

摘要："BackgroundTreatment 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.MethodsHerein, 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 Ti-PDA@SNP-OGP. The 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-beta-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.ResultsTi-PDA@SNP-OGP displayed a synergistic photothermal and NO-dependent antibacterial effect against MRSA following near-infrared light 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 components (P < 0.01). In vitro experiments revealed that Ti-PDA@SNP-OGP not only facilitated osteogenic differentiation of MSCs, but also promoted the polarization of pro-inflammatory M1 macrophages to the anti-inflammatory M2-phenotype (P < 0.05 or P < 0.01). The favorable osteo-immune microenvironment further facilitated osteogenesis of MSCs and the anti-inflammation of RAW264.7 cells via multiple paracrine signaling pathways (P < 0.01). In vivo evaluation confirmed the aforementioned results and revealed that Ti-PDA@SNP-OGP induced ameliorative osseointegration in an MRSA-infected femoral defect implantation model (P < 0.01).ConclusionsThese findings suggest that Ti-PDA@SNP-OGP is a promising multi-functional material for the high-efficient treatment of MRSA infections in implant replacement surgeries."

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