Implant-associated bacterial infections significantly impair the integration between titanium and soft tissues. Traditional antibacterial modifications of titanium implants are able to eliminate bacteria, but the resulting pro-inflammatory reactions are usually ignored, which still poses potential risks to human bodies. Here, a dual drug-loading system on titanium has been developed via the adhesion of a catechol motif-modified methacrylated gelatin hydrogel onto TiO₂ nanotubes. Then synthesized CaO₂ nanoparticles (NPs) are embedded into the hydrogel, and interleukin-4 (IL-4) is loaded into the nanotubes to achieve both antibacterial and anti-inflammatory properties. The dual drug-loading system can eliminate Staphylococcus aureus (S. aureus) rapidly, attributed to the H₂O₂ release from CaO₂ NPs. The potential cytotoxicity of CaO₂ NPs is also remarkably reduced after being embedded into the hydrogel. More importantly, with the gradual release of IL-4, the dual drug-loading system is capable of modulating pro-inflammatory reactions by inducing M2 phenotype polarization of macrophages. In a subcutaneous infection model, the S. aureus contamination is effectively resolved after 2 days, and the resulting pro-inflammatory reactions are also inhibited after 7 days. Finally, the damaged tissue is significantly recovered. Taken together, the dual drug-loading system exhibits great therapeutic potential in effectively killing pathogens and inhibiting the resulting pro-inflammatory reactions.

中文翻译：

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过氧化钙纳米颗粒包埋在抗炎 TiO2 纳米管上的涂层用于杀菌和改善炎症环境

种植体相关的细菌感染显着损害了钛和软组织之间的整合。传统的钛植入物抗菌修饰能够消除细菌，但由此产生的促炎反应通常被忽视，这仍然对人体构成潜在风险。在这里，通过将儿茶酚基序修饰的甲基丙烯酸化明胶水凝胶粘附到 TiO ₂纳米管上，开发了钛双载药系统。然后将合成的 CaO ₂纳米粒子 (NPs) 嵌入水凝胶中，并将白细胞介素-4 (IL-4) 加载到纳米管中以实现抗菌和抗炎特性。双载药系统可消除金黄色葡萄球菌（S. aureus) 迅速，归因于从 CaO ₂ NPs释放H ₂ O ₂。嵌入水凝胶后，CaO ₂ NPs的潜在细胞毒性也显着降低。更重要的是，随着 IL-4 的逐渐释放，双重载药系统能够通过诱导巨噬细胞的 M2 表型极化来调节促炎反应。在皮下感染模型中，金黄色葡萄球菌2天后污染得到有效解决，7天后产生的促炎反应也得到抑制。最后，受损组织得到显着恢复。总之，双重载药系统在有效杀死病原体和抑制由此产生的促炎反应方面表现出巨大的治疗潜力。