Department of Orthopaedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai 200233, China.
Centre for Translational Bone, Joint and Soft Tissue Research, University Hospital and Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden 01307, Germany.
Acta Biomater. 2019 Apr 15;89:403-418. doi: 10.1016/j.actbio.2019.03.027. Epub 2019 Mar 15.
Tantalum (Ta) has been shown to enhance osseointegration in clinical practice, yet little is known about whether Ta nanofilms can be used as antimicrobial coatings in vivo. A highly biocompatible Ta nanofilm was developed using magnetron sputtering technology to further study the mechanism of its antibacterial effects in vivo and elucidate its potential for clinical translation. The Ta nanofilms exhibited effective antimicrobial activity against soft tissue infections but did not show an intrinsic antimicrobial effect in vitro. This inconsistency between the in vivo and in vitro antimicrobial effects was further investigated using ex vivo models. The Ta nanofilms could enhance the phagocytosis of bacteria by polymorphonuclear neutrophils (PMNs, neutrophils), reduce the lysis of neutrophils and enhance the proinflammatory cytokine release of macrophages. This accumulative enhancement of the local host defenses contributed to the favorable antibacterial effect in vivo. The alleviated osteolysis observed in the presence of the Ta nanofilms in the osteomyelitis model further proved the practicality of this antibacterial strategy in the orthopedic field. In summary, Ta nanofilms show excellent biocompatibility and in vivo antimicrobial activity mediated by the enhancement of local innate immunity and are promising for clinical application. STATEMENT OF SIGNIFICANCE: In this study, Ta nanofilms were deposited on titanium substrate by magnetron sputtering. Ta nanofilms exhibited excellent in vivo and in vitro biocompatibility. In vivo antimicrobial effects of Ta nanofilms were revealed by soft tissue infection and osteomyelitis models, while no direct antibacterial activity was observed in vitro. Comprehensive ex vivo models revealed that Ta nanofilms could enhance the phagocytosis of bacteria by neutrophils, reduce the lysis of neutrophils and promote the release of proinflammatory cytokines from macrophages. This immunomodulatory effect helps host to eliminate bacteria. In contrast to traditional antimicrobial nanocoatings which apply toxic materials to kill bacteria, this work proposes a safe, practical and effective Ta nanofilm immunomodulatory antimicrobial strategy with clinical translational prospect.
钽 (Ta) 已被证明可增强临床实践中的骨整合，然而，对于 Ta 纳米薄膜是否可作为体内抗菌涂层尚知之甚少。本研究采用磁控溅射技术开发了一种高生物相容性 Ta 纳米薄膜，以进一步研究其体内抗菌作用机制，并阐明其在临床转化方面的潜力。Ta 纳米薄膜对软组织感染具有有效的抗菌活性，但在体外没有表现出固有抗菌作用。这种体内和体外抗菌作用之间的不一致性，通过离体模型进一步进行了研究。Ta 纳米薄膜可增强多形核粒细胞 (PMN，中性粒细胞) 对细菌的吞噬作用，减少中性粒细胞的溶解，并增强巨噬细胞的促炎细胞因子释放。这种局部宿主防御能力的累积增强有助于实现体内有利的抗菌效果。在骨髓炎模型中存在 Ta 纳米薄膜时观察到的骨溶解减轻进一步证明了这种抗菌策略在骨科领域的实用性。总之，Ta 纳米薄膜表现出优异的生物相容性和体内抗菌活性，这种活性是通过增强局部固有免疫介导的，具有临床应用的前景。
