The poor efficiency of US-responsive coatings on implants restricts their practical application. Immunotherapy that stimulates immune cells to enhance their antibacterial activity is expected to synergize with sonodynamic therapy for treating implant infection effectively and safely. Herein, US-responsive hybrid coatings composed of the oxygen-deficient BaTiO nanorod arrays and -arginine (BaTiO/LA) are designed and prepared on titanium implants for sonocatalytic therapy-cooperated immunotherapy to treat Methicillin-resistant (MRSA) infection. BaTiO/LA can generate more oxidizing reactive oxygen species (ROS, hydroxyl radical (·OH)) and reactive nitrogen species (RNS, peroxynitrite anion (ONOO)). The construction of nanorod arrays and oxygen defects balances the piezoelectric properties and sonocatalytic capability during US treatment. The generated piezoelectric electric field provides a sufficient driving force to separate electrons and holes, and the oxygen defects attenuate the electron-hole recombination efficiency, consequently increasing the yield of ROS during the US treatment. Moreover, nitric oxide (NO) released by -arginine reacts with the superoxide radical (·O) to produce ONOO. Since, this radical chain reaction improves the oxidizing ability between bacteria and radicals, the cell membrane (argB, secA2) and DNA (dnaBGXN) are destroyed. The bacterial self-repair mechanism indirectly accelerates bacterial death based on the transcriptome analysis. In addition to participating in the radical chain reaction, NO positively affects macrophage M1 polarization to yield potent phagocytosis to MRSA. As a result, without introducing an extra sonosensitizer, BaTiO/LA exhibits excellent antibacterial activity against MRSA after the US treatment for 15 min. Furthermore, BaTiO/LA facilitates macrophage M2 polarization after implantation and improves osteogenic differentiation. The combined effects of sonodynamic therapy and immunoregulation lead to an effective and safe treatment method for implant-associated infections.

中文翻译：

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超声波驱动的自由基链反应和压电混合涂层的免疫调节治疗植入物感染

植入物上的US响应涂层的低效率限制了其实际应用。刺激免疫细胞增强抗菌活性的免疫疗法有望与声动力疗法协同作用，有效、安全地治疗植入物感染。在此，在钛植入物上设计并制备了由缺氧 BaTiO 纳米棒阵列和精氨酸 (BaTiO/LA) 组成的 US 响应混合涂层，用于声催化疗法配合免疫疗法治疗耐甲氧西林 (MRSA) 感染。 BaTiO/LA可以产生更多的氧化活性氧（ROS，羟基自由基（·OH））和活性氮（RNS，过氧亚硝酸根阴离子（ONOO））。纳米棒阵列和氧缺陷的构造平衡了超声波处理过程中的压电特性和声催化能力。产生的压电电场提供了足够的驱动力来分离电子和空穴，并且氧缺陷削弱了电子-空穴复合效率，从而增加了US处理期间ROS的产率。此外，β-精氨酸释放的一氧化氮（NO）与超氧自由基（·O）反应生成ONOO。由于这种自由基链式反应提高了细菌和自由基之间的氧化能力，因此细胞膜（argB、secA2）和DNA（dnaBGXN）被破坏。根据转录组分析，细菌的自我修复机制间接加速了细菌的死亡。除了参与自由基链式反应外，NO 还积极影响巨噬细胞 M1 极化，从而对 MRSA 产生有效的吞噬作用。因此，在不引入额外声敏剂的情况下，BaTiO/LA 在超声处理 15 分钟后对 MRSA 表现出优异的抗菌活性。此外，BaTiO/LA 促进植入后巨噬细胞 M2 极化并改善成骨分化。声动力疗法和免疫调节的综合作用为种植体相关感染提供了一种有效且安全的治疗方法。