Tracking and eradicating Staphylococcus aureus in the periprosthetic microenvironment are critical for preventing periprosthetic joint infection (PJI), yet effective strategies remain elusive. Here, we report an implant nanoparticle coating that locoregionally yields bactericidal super chimeric antigen receptor macrophages (CAR-MΦs) to prevent PJI. We demonstrate that the plasmid-laden nanoparticle from the coating can introduce S. aureus –targeted CAR genes and caspase-11 short hairpin RNA (CASP11 shRNA) into macrophage nuclei to generate super CAR-MΦs in mouse models. CASP11 shRNA allowed mitochondria to be recruited around phagosomes containing phagocytosed bacteria to deliver mitochondria-generated bactericidal reactive oxygen species. These super CAR-MΦs targeted and eradicated S. aureus and conferred robust bactericidal immunologic activity at the bone-implant interface. Furthermore, the coating biodegradability precisely matched the bone regeneration process, achieving satisfactory osteogenesis. Overall, our work establishes a locoregional treatment strategy for priming macrophage-specific bactericidal immunity with broad application in patients suffering from multidrug-resistant bacterial infection.

中文翻译：

---

表面纳米沉积局部产生杀菌超级CAR-巨噬细胞加速假体周围骨整合

追踪并根除金黄色葡萄球菌假体周围微环境中的微环境对于预防假体周围关节感染（PJI）至关重要，但有效的策略仍然难以捉摸。在此，我们报道了一种植入物纳米颗粒涂层，该涂层可在局部区域产生杀菌性超级嵌合抗原受体巨噬细胞（CAR-MΦs）以预防 PJI。我们证明，来自涂层的载有质粒的纳米颗粒可以引入金黄色葡萄球菌– 将 CAR 基因和 caspase-11 短发夹 RNA (CASP11 shRNA) 靶向巨噬细胞核，在小鼠模型中生成超级 CAR-MΦ。CASP11 shRNA 允许线粒体在含有吞噬细菌的吞噬体周围募集，以传递线粒体产生的杀菌活性氧。这些超级 CAR-MΦ 被针对性地消灭金黄色葡萄球菌并在骨-植入物界面赋予强大的杀菌免疫活性。此外，涂层的生物降解性与骨再生过程精确匹配，实现了令人满意的成骨效果。总的来说，我们的工作建立了一种局部治疗策略，用于启动巨噬细胞特异性杀菌免疫，并广泛应用于患有多重耐药细菌感染的患者。