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Elimination of methicillin-resistant
Staphylococcus aureus biofilms on titanium implantsvia photo-thermally-triggered nitric oxide and immunotherapy for enhanced osseointegration- Military Medical Research Vol. 11, Issue 2, Pages: 157-179(2024)
- Affiliations：
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
- Author bio：
*yuyonglin@zmu.edu.cn
kiki-happy@263.net
taobailong@hospital.cqmu.edu.cn
jiaoyang1989731@163.com
- Funds：
DOI：10.1186/s40779-023-00454-y
CLC：-
Published：2024-04
- Accepted：
Scan QR Code
Cite this article as: Yu YL, Wu JJ, Lin CC, Qin X, Tay FR, Miao L, et al. Elimination of methicillin-resistant Staphylococcus aureus biofilms on titanium implants via photothermally-triggered nitric oxide and immunotherapy for enhanced osseointegration. Mil Med Res. 2023;10(1):21.
Cite this article as: Yu YL, Wu JJ, Lin CC, Qin X, Tay FR, Miao L, et al. Elimination of methicillin-resistant Staphylococcus aureus biofilms on titanium implants via photothermally-triggered nitric oxide and immunotherapy for enhanced osseointegration. Mil Med Res. 2023;10(1):21. DOI： 10.1186/s40779-023-00454-y.
摘要
Abstract
Background:
2
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:
2
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 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.
Results:
2
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 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).
Conclusions:
2
Ti-PDA@SNP-OGP is a promising multi-functional material for the high-efficient treatment of MRSA infections in implant replacement surgeries.
关键词
Keywords
references
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