Fan Mengke, Ren Youliang, Zhu Yanbin, Zhang Hao, Li Shuaijie, Liu Chunyu, Lv Hongzhi, Chu Lei, Hou Zhiyong, Zhang Yingze, Pan Haobo, Cui Xu, Chen Wei
Department of Orthopaedic Surgery the Hebei Medical University Third Hospital, Orthopaedic Research Institution of Hebei Province, NHC Key Laboratory of Intelligent Orthopaedic Equipment, Engineering Research Center of Orthopedic Minimally Invasive Intelligent Equipment of Ministry of Education, Key Laboratory of Biomechanics of Hebei Province, No.139 Ziqiang Road, Shijiazhuang, 050051, PR China.
Shenzhen Key Laboratory of Marine Biomedical Materials, CAS-HK Joint Lab of Biomaterials, The Key Laboratory of Biomedical Imaging Science and System, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, PR China.
Bioact Mater. 2024 Oct 18;44:184-204. doi: 10.1016/j.bioactmat.2024.10.009. eCollection 2025 Feb.
Bone infection is a catastrophe in clinical orthopedics. Despite being the standard therapy for osteomyelitis, antibiotic-loaded polymethyl methacrylate (PMMA) cement has low efficiency against bacteria in biofilms. Furthermore, high-dose antibiotic-loaded implants carry risks of bacterial resistance, tissue toxicity, and impairment of local tissue healing. By incorporating borosilicate bioactive glass (BSG) into low-dose gentamicin sulfate (GS)-loaded PMMA cement, an intelligent strategy that synergistically eradicates bacteria and sequentially promotes osseointegration, was devised. Results showed that BSG did not compromises the handling properties of the cement, but actually endowed it with an ionic and alkaline microenvironment, thereby damaging the integrity of bacterial cell walls and membranes, inhibiting ATP synthesis by disrupting the respiratory chain in cell membranes and glycogen metabolism, and elevating reactive oxygen species (ROS) levels by weakening antioxidant components (peroxisomes and carotenoids). These antibacterial characteristics of BSG synergistically reinforced the effectiveness of GS, which was far below the actual clinical dosage, achieving efficient bacterial killing and biofilm clearance by binding to the 30S subunit of ribosomes. Furthermore, the released GS and the ionic and alkaline microenvironment from the implants fostered the osteogenic activity of hBMSCs and coordinately enhanced osseointegration . Collectively, this study underscores that BSG incorporation offers a promising strategy for reducing antibiotic dosage while simultaneously enhancing the antibacterial activity and osteogenesis of implants. This approach holds potential for resolving the conflict between bacterial resistance and bone infection.
骨感染是临床骨科中的一大难题。尽管载抗生素的聚甲基丙烯酸甲酯（PMMA）骨水泥是治疗骨髓炎的标准疗法，但对生物膜中的细菌杀菌效率较低。此外，高剂量载抗生素植入物存在细菌耐药、组织毒性和局部组织愈合受损的风险。通过将硼硅酸盐生物活性玻璃（BSG）掺入低剂量硫酸庆大霉素（GS）载PMMA骨水泥中，设计了一种协同根除细菌并依次促进骨整合的智能策略。结果表明，BSG并未损害骨水泥的操作性能，反而赋予其离子和碱性微环境，从而破坏细菌细胞壁和细胞膜的完整性，通过破坏细胞膜中的呼吸链和糖原代谢抑制ATP合成，并通过削弱抗氧化成分（过氧化物酶体和类胡萝卜素）提高活性氧（ROS）水平。BSG的这些抗菌特性协同增强了远低于实际临床剂量的GS的有效性，通过与核糖体的30S亚基结合实现高效杀菌和生物膜清除。此外，植入物释放的GS以及离子和碱性微环境促进了人骨髓间充质干细胞（hBMSCs）的成骨活性，并协同增强了骨整合。总的来说，这项研究强调，掺入BSG为减少抗生素用量同时增强植入物的抗菌活性和成骨作用提供了一种有前景的策略。这种方法有望解决细菌耐药与骨感染之间的矛盾。
