首页|抗菌性碳点修饰PEEK干预MRSA感染环境植入物骨整合性能的体内研究

抗菌性碳点修饰PEEK干预MRSA感染环境植入物骨整合性能的体内研究

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目的 本研究拟评价抗菌性碳点修饰聚醚醚酮(polyether ether ketone,PEEK)在感染性骨缺损环境的骨整合性能。方法 熔融法制备结合透析纯化获得胍基碳点(guanidine-based carbon dots,G-CDs),应用聚乙烯醇缩丁醛酯(polyvinyl butyral,PVB)通过浸泡-干燥法制备G-CDs修饰的PEEK植入物(PEEK/PVB-G-CDs)。将SD大鼠分为:PEEK植入未感染组(PEEK(-)组),PEEK/PVB-G-CDs植入未感染组(PEEK/PVB-G-CDs(-)组),PEEK植入感染组(PEEK(+)组),PEEK/PVB-G-CDs植入感染组(PEEK/PVB-G-CDs(+)组)。每组大鼠均于垂直股骨外侧髁处制备一个直径2 mm、深度5 mm的孔洞以模拟骨缺损。将30 μL生理盐水注入PEEK(-)组和PEEK/PVB-G-CDs(-)组大鼠骨缺损的骨髓腔内形成未感染组。将30 μL耐甲氧西林金黄色葡萄球菌(Methicillin-resistant Staphylococcus aureus,MRSA)菌悬液(1。5 × 104 CFU/mL)注入 PEEK(+)组和 PEEK/PVB-G-CDs(+)组大鼠骨缺损的骨髓腔内。植入术后0、2和4周,应用动物专用X射线机照射各组大鼠植入部位。术后6周,Micro-CT评估植入部位的骨组织特征。骨髓细菌培养、苏木精-伊红染色(HE staining)、甲苯胺蓝染色(Toluidine blue staining)、戈德纳三色染色(Goldner trichrome staining)及免疫组化染色分析各组大鼠的骨植入部位。结果 (1)X射线、Micro-CT、骨髓细菌培养和组织病理学分析等结果确定证实了 PEEK(-)组和PEEK/PVB-G-CDs(-)组未出现感染与骨缺损整合;PEEK/PVB-G-CDs(+)组发挥抗菌性有效控制MRSA,菌株形成的骨髓炎实现骨整合,而PEEK(+)组因持续的感染无法骨整合;(2)免疫组化染色评价明确PEEK(+)组显示出比其他3组更低的白细胞介素(interleukin,IL)-4和IL-10等抗炎因子以及更强的IL-6和肿瘤坏死因子(tumor necrosis factor,TNF)-α等促炎因子表达,表明G-CDs修饰的PEEK可抑制MRSA感染,调节局部微环境的炎症水平,促进骨缺损部位的骨整合。结论 抗菌性碳点修饰PEEK具备优异的骨整合性能,为今后的临床治疗提供了一种候选策略。
In vivo study of antibacterial carbon dot-modified polyether ether ketone to improve osseointegration of implants for treating MRSA infection environments
Objective This study aimed to evaluate the bone integration performance of antibacterial carbon dot(CD)-modified polyether ether ketone(PEEK)in infectious bone defect environments.Methods Guanidine-based CDs(G-CDs)prepared by the melting method combined with dialysis purification were used to modify PEEK implants using polyvinyl butyraldehyde(PVB)by the soaking-drying method(PEEK/PVB-G-CDs).SD rats were divided into the following groups:(1)PEEK-implanted uninfected(PEEK(-)),(2)PEEK/PVB-G-CDs-implanted uninfected(PEEK/PVB-G-CDs(-)),(3)PEEK-implanted infected(PEEK(+)),and(4)PEEK/PVB-G-CDs-implanted infected(PEEK/PVB-G-CDs(+)).A hole(diameter 2 mm,depth 5 mm)was drilled at the lateral condyle of the vertical femur in all rats to simulate a bone defect.Rats in the PEEK(-)and PEEK/PVB-G-CDs(-)groups without infection were injected with 30 μL physiological saline into the bone marrow cavity,and rats in the PEEK(+)and PEEK/PVB-G-CDs(+)groups with infection were injected with 30 μL MRSA bacterial suspension(1.5 × 104 colony-forming units/mL)into the bone marrow cavity.The implantation site was observed using animal-specific X-ray examination at 0,2,and 4 weeks after implantation,and the bone tissue characteristics of the implantation site were evaluated by micro computed tomography(CT)at 6 weeks after surgery.The bone implantation sites in each group of rats were examined by bacterial culture of bone marrow and hematoxylin and eosin staining,Toluidine blue,Goldner trichrome,and immunohistochemical staining.Results X-ray,Micro-CT,bacterial culture of bone marrow,and histopathological analysis confirmed no signs of infection in the PEEK(-)and PEEK/PVB-G-CDs(-)groups and the implants were integrated with the bone defects.Rats in the PEEK/PVB-G-CDs(+)group showed signs of antibacterial activity that effectively controlled the osteomyelitis caused by MRSA and achieved bone integration,while rats in the PEEK(+)group failed to achieve bone integration because of persistent infection.Immunohistochemical staining confirmed lower levels of anti-inflammatory factors such as IL-4 and IL-10 in the PEEK(+)group,and stronger expression of pro-inflammatory factors such as IL-6 and TNF-α compared with the other three groups,indicating that G-CD-modified PEEK inhibited MRSA infection,regulated inflammation levels in the local microenvironment,and promoted bone integration at the site of bone defects.Conclusions Antibacterial G-CDs modified PEEK exhibits excellent bone integration performance,providing a candidate strategy for future clinical treatment of infectious bone defects.

antibacterial carbon dotsPEEKimplant modificationosseointergrationMRSA infection

何宏星、张心恬、章梦涵、王耀、邓晓琴、翁少煌

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福建医科大学实验动物中心,福州 350122

福建医科大学药学院,福州 350122

抗菌性碳点 聚醚醚酮 植入物改性 骨整合 MRSA感染

2024

中国实验动物学报
中国实验动物学会,中国医学科学院医学实验动物研究所

中国实验动物学报

CSTPCD北大核心
影响因子:0.767
ISSN:1005-4847
年,卷(期):2024.32(11)