Multi‐Mode Antibacterial Strategies Enabled by Gene‐Transfection and Immunomodulatory Nanoparticles in 3D‐Printed Scaffolds for Synergistic Exogenous and Endogenous Treatment of Infections
Multi‐Mode Antibacterial Strategies Enabled by Gene‐Transfection and Immunomodulatory Nanoparticles in 3D‐Printed Scaffolds for Synergistic Exogenous and Endogenous Treatment of Infections
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DOI：
10.1002/adma.202200096
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发表时间：
2022-03
影响因子：
29.4
通讯作者：
X. Qu;Minqi Wang;Miaochen Wang;Haozheng Tang;Shutao Zhang;Hongtao Yang;Weien Yuan;You Wang;Jianping Yang;B. Yue
中科院分区：
文献类型：
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作者：
X. Qu;Minqi Wang;Miaochen Wang;Haozheng Tang;Shutao Zhang;Hongtao Yang;Weien Yuan;You Wang;Jianping Yang;B. Yue
随着对难治性金黄色葡萄球菌相关植入物感染的研究不断深入，仍然存在一些挑战，包括感染区域内抗生素浓度低、细胞内细菌实现的免疫逃逸、骨髓源性抑制细胞（MDSC）诱导区域免疫抑制以及药物悬浮后残留病原菌的复发。在此，提出了一种同时解决这些问题的新型抗菌系统。具体来说，设计了一种具有壳核纳米颗粒的氧物种响应3D打印支架，该支架负载有抗菌肽质粒（LL37质粒），并在其表面嫁接了LL37（LL37@ZIF8-LL37）。表面移植的 LL37 直接杀死金黄色葡萄球菌，进入细胞后，纳米颗粒杀死细胞内细菌。此外，在体外和体内，LL37质粒翻译后，细胞充当抗菌肽的工厂，从而在感染部位产生持续、持久的抗菌作用。该系统显着减少了受感染微环境中MDSC的异常增加，从而缓解免疫抑制状态并恢复保护性抗菌免疫反应。因此，该抗菌系统通过提供组合的活性抗菌和免疫治疗策略，为金黄色葡萄球菌相关感染提供了抗菌免疫反应和新策略，从而显着降低了种植体相关感染恢复后的复发率。
As research on refractory Staphylococcus aureus‐related implant infection intensifies, certain challenges remain, including low antibiotic concentrations within infected areas, immune escape achieved by intracellular bacteria, myeloid‐derived suppressor cells (MDSCs) inducing regional immunosuppression, and recurrence of residual pathogenic bacteria after drug suspension. Herein, a novel antimicrobial system to simultaneously address these issues is proposed. Specifically, an oxygen‐species‐responsive 3D‐printed scaffold with shell–core nanoparticles is designed, which are loaded with an antimicrobial peptide plasmid (LL37 plasmid) and have LL37 grafted on their surface (LL37@ZIF8‐LL37). The surface‐grafted LL37 directly kills S. aureus and, following entry into cells, the nanoparticles kill intracellular bacteria. Moreover, in vitro and in vivo, following translation of the LL37 plasmid, cells function as factories of the antimicrobial peptide, thereby generating a continuous, prolonged antibacterial effect at the site of infection. This system significantly reduces the abnormal increase in MDSCs within the infected microenvironment, thus relieving the immunosuppressive state and restoring a protective antimicrobial immune response. Hence, this proposed antimicrobial system provides an antimicrobial immune response and a novel strategy for S. aureus‐related infections by offering a combined active antimicrobial and immunotherapeutic strategy, thereby significantly reducing the recurrence rate following recovery from implant‐associated infections.