Implant-associated infections (IAIs) pose a significant threat to orthopedic surgeries. Bacteria colonizing the surface of implants disrupt bone formation-related cells and interfere with the osteoimmune system, resulting in an impaired immune microenvironment and osteogenesis disorders. Inspired by nature, a zeolitic imidazolate framework (ZIF)-sealed smart drug delivery system on Ti substrates (ZSTG) was developed for the “natural-artificial dual-enzyme intervention (NADEI)” strategy to address these challenges. The subtle sealing design of ZIF-8 on the TiO nanotubes ensured glucose oxidase (GOx) activity and prevented its premature leakage. In the acidic infection microenvironment, the degradation of ZIF-8 triggered the rapid release of GOx, which converted glucose into HO for disinfection. The Zn released from degraded ZIF-8, as a DNase mimic, can hydrolyze extracellular DNA, which further enhances HO-induced disinfection and prevents biofilm formation. Importantly, Zn-mediated M2 macrophage polarization significantly improved the impaired osteoimmune microenvironment, accelerating bone repair. Transcriptomics revealed that ZSTG effectively suppressed the inflammatory cascade induced by lipopolysaccharide while promoting cell proliferation, homeostasis maintenance, and bone repair. and results confirmed the superior anti-infective, osteoimmunomodulatory, and osteointegrative capacities of the ZSTG-mediated NADEI strategy. Overall, this smart bionic platform has significant potential for future clinical applications to treat IAIs.

中文翻译：

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蜂窝状 ZIF 密封界面通过抗感染和骨免疫调节增强骨整合

种植体相关感染（IAI）对骨科手术构成重大威胁。植入物表面的细菌会破坏骨形成相关细胞并干扰骨免疫系统，导致免疫微环境受损和成骨障碍。受大自然的启发，针对“天然-人工双酶干预（NADEI）”策略，开发了钛基底上沸石咪唑酯框架（ZIF）密封的智能药物递送系统（ZSTG）来应对这些挑战。 ZIF-8 在 TiO 纳米管上的微妙密封设计确保了葡萄糖氧化酶 (GOx) 的活性并防止其过早泄漏。在酸性感染微环境中，ZIF-8的降解引发GOx的快速释放，将葡萄糖转化为H2O进行消毒。降解的 ZIF-8 释放的 Zn 作为 DNase 模拟物，可以水解细胞外 DNA，进一步增强 H2O 诱导的消毒并防止生物膜形成。重要的是，锌介导的 M2 巨噬细胞极化显着改善受损的骨免疫微环境，加速骨修复。转录组学显示，ZSTG 有效抑制脂多糖诱导的炎症级联反应，同时促进细胞增殖、稳态维持和骨修复。结果证实了 ZSTG 介导的 NADEI 策略具有卓越的抗感染、骨免疫调节和骨整合能力。总体而言，这个智能仿生平台在未来治疗 IAI 的临床应用中具有巨大的潜力。