Zhou Hang, Ren Youliang, Zou Kaixiong, Jin Ying, Liu Hang, Jiang Haitao, Shi Lei, Sheng Xiaomin, Weeks Jason, Wang Hannah, Xue Thomas, Schwarz Edward M, Xie Chao, Deng Zhongliang, Wang Lin, Chu Lei
Department of Orthopaedics, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, P. R. China.
National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou, 510006, P. R. China.
Adv Healthc Mater. 2025 Jan;14(3):e2403261. doi: 10.1002/adhm.202403261. Epub 2024 Nov 27.
Implant-associated Staphylococcus aureus (S. aureus) osteomyelitis (IASO) leads to high orthopedic implant failure rates due to the formation of Staphylococcal abscess community within the bone marrow and bacterial colonization in the osteocyte lacuno-canalicular network (OLCN). To address this, antimicrobial peptides (HHC36)-loaded titania nanotubes (NTs) are developed on titanium screws (Ti-NTs-P-A), which integrate pH-responsive polymethacrylic acid to control HHC36 release for eradicating bacteria in IASO. Colony-forming unit assay confirmed that Ti-NTs-P-A screws maintained sustainable antibacterial effectiveness, killing over 65% of S. aureus even after multiple bacterial solution replacements. Notably, Ti-NTs-P-A screws exhibit significant pH-responsive HHC36 release behavior and bactericidal activity, consistent with the phenotype of peptides-killed bacteria from scanning electron microscopy. Transcriptome sequencing results reveal that Ti-NTs-P-A screws interfered with ribosome formation and disrupted the arginine biosynthesis, which is crucial for bacterial survival in acidic environments. In the non-infected implant model, the bone-implant contact ratio of the Ti-NTs-P-A screw is 2.3 times that of the clinically used titanium screw. In an IASO model, Ti-NTs-P-A screws effectively eradicated bacteria within the OLCN, achieving an 80% infection control rate and desirable osteointegration. Collectively, Ti-NTs-P-A screws with pH-responsive antibacterial properties exhibit great potential for eradicating bacteria and achieving osseointegration in IASO.
植入相关的金黄色葡萄球菌骨髓炎（IASO）由于骨髓内葡萄球菌脓肿群落的形成以及骨细胞腔管网络（OLCN）中的细菌定植，导致骨科植入物的失败率很高。为了解决这个问题，在钛螺钉（Ti-NTs-P-A）上开发了负载抗菌肽（HHC36）的二氧化钛纳米管（NTs），其整合了pH响应性聚甲基丙烯酸以控制HHC36的释放，从而根除IASO中的细菌。菌落形成单位测定证实，Ti-NTs-P-A螺钉保持了可持续的抗菌效果，即使在多次更换细菌溶液后仍能杀死超过65%的金黄色葡萄球菌。值得注意的是，Ti-NTs-P-A螺钉表现出显著的pH响应性HHC36释放行为和杀菌活性，这与扫描电子显微镜下肽杀死细菌的表型一致。转录组测序结果表明，Ti-NTs-P-A螺钉干扰了核糖体的形成并破坏了精氨酸生物合成，而精氨酸生物合成对细菌在酸性环境中的存活至关重要。在未感染的植入模型中，Ti-NTs-P-A螺钉的骨-植入物接触率是临床使用的钛螺钉的2.3倍。在IASO模型中，Ti-NTs-P-A螺钉有效地根除了OLCN内的细菌，实现了80%的感染控制率和理想的骨整合。总的来说，具有pH响应抗菌特性的Ti-NTs-P-A螺钉在根除IASO中的细菌和实现骨整合方面具有巨大潜力。
