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

Military Medical Research

Research

Chuan-Chuan Lin¹  Yong-Lin Yu²  Xian Qin³  Yang Jiao⁴  Li Miao⁴  Jun-Jie Wu⁵  Bai-Long Tao⁵  Franklin R. Tay⁶ 

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

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

DOI  :  10.1186/s40779-023-00454-y

 received in 2022-05-19, accepted in 2023-04-07,  发布年份 2023

来源: Springer

【 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-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.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.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

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Fig. 7