Bohn Maja Charlotte, Oltmanns Hilke, Meißner Jessica
Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine Hannover, Hanover, Germany.
Front Bioeng Biotechnol. 2025 Sep 10;13:1661383. doi: 10.3389/fbioe.2025.1661383. eCollection 2025.
Periprosthetic joint infections (PJIs) are severe complications following surgical joint replacement and one of the main reasons for implant failure in human and veterinary medicine. Due to the global rise in antibiotic resistances and failure to prevent and treat PJIs, it is necessary to identify new antibacterial substances for the management of these infections. Methylglyoxal (MGO) is a dicarbonyl compound that has been identified as the main antibacterial component in Manuka honey. The aim of the study was to evaluate the suitability of MGO as an additive to polymethylmethacrylate bone cement in connection to PJIs. To test the antibacterial activity of pure MGO and MGO-containing bone cement against clinical isolates of , minimal inhibitory concentrations (MICs) were determined, growth of bacteria on bone cement was visualized, and the influence on infection of human osteosarcoma (HOS) cells was examined. Cytotoxicity of pure MGO and MGO-containing bone cement against HOS cells was analyzed with viability and proliferation assays, staining of cells on bone cement surface, and measurement of Interleukin-6 (IL-6) release. Activation of p38 MAP kinase was analyzed using Western blotting. MGO inhibited growth of at 0.15 mg/mL, reduced bacterial colonization of bone cement at 25 mg per bone cement platelet, and reduced infection of HOS cells at 0.05 mg/mL. The IC of pure MGO for cell viability was 0.17 mg/mL. At higher concentrations, bone cement with MGO reduced viability and proliferation, but did not cause IL-6 release. Western blots revealed p38 activation following MGO treatment, indicating involvement of the p38 pathway in stress reactions due to the treatment. Taken together, effectiveness of MGO against PJI-relevant could be shown but biocompatibility was limited and further research is necessary to enhance biocompatibility.
人工关节周围感染（PJI）是外科关节置换术后的严重并发症，也是人类和兽医学中植入物失败的主要原因之一。由于全球抗生素耐药性的上升以及预防和治疗PJI的失败，有必要识别新的抗菌物质来管理这些感染。甲基乙二醛（MGO）是一种二羰基化合物，已被确定为麦卢卡蜂蜜中的主要抗菌成分。本研究的目的是评估MGO作为聚甲基丙烯酸甲酯骨水泥添加剂与PJI相关的适用性。为了测试纯MGO和含MGO的骨水泥对临床分离株的抗菌活性，测定了最低抑菌浓度（MIC），观察了细菌在骨水泥上的生长情况，并检测了对人骨肉瘤（HOS）细胞感染的影响。通过活力和增殖测定、骨水泥表面细胞染色以及白细胞介素-6（IL-6）释放的测量，分析了纯MGO和含MGO的骨水泥对HOS细胞的细胞毒性。使用蛋白质印迹法分析p38丝裂原活化蛋白激酶的激活情况。MGO在0.15mg/mL时抑制了[具体细菌名称未给出]的生长，在每片骨水泥含25mg时减少了骨水泥上的细菌定植，在0.05mg/mL时减少了HOS细胞的感染。纯MGO对细胞活力的半数抑制浓度（IC）为0.17mg/mL。在较高浓度下，含MGO的骨水泥降低了活力和增殖，但未引起IL-6释放。蛋白质印迹显示MGO处理后p38活化，表明p38途径参与了该处理引起的应激反应。综上所述，MGO对与PJI相关的[具体细菌名称未给出]具有有效性，但生物相容性有限，需要进一步研究以提高生物相容性。
