Advanced antibacterial activity of biocompatible tantalum nanofilm via enhanced local innate immunity

• Published in: Acta biomaterialia 2019-04, Vol.89, p.403-418
• Main Authors: Yang, Chuang, Li, Jinhua, Zhu, Chongzun, Zhang, Qixuan, Yu, Jinlong, Wang, Jiaxing, Wang, Qiaojie, Tang, Jin, Zhou, Huaijuan, Shen, Hao
• Format: Article
• Language: English
• Subjects: Animals; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antibacterial; Antibacterial activity; Antimicrobial activity; Antimicrobial agents; Bacteria; Biocompatibility; Biomedical materials; Coated Materials, Biocompatible - chemistry; Coated Materials, Biocompatible - pharmacology; Cytokines; Immunity; Immunity, Innate - drug effects; Immunomodulation; Immunomodulatory effect; In vivo methods and tests; Infections; Inflammation; Innate immunity; Leukocytes (neutrophilic); Leukocytes (polymorphonuclear); Lysis; Macrophages; Magnetron sputtering; Membranes, Artificial; Mice; Mice, Inbred BALB C; Nanostructures - chemistry; Neutrophils; Neutrophils - immunology; Neutrophils - microbiology; Neutrophils - pathology; Osseointegration; Osteolysis; Osteomyelitis; Phagocytosis; Soft tissues; Substrates; Surgical implants; Ta nanofilm; Tantalum; Tantalum - chemistry; Tantalum - pharmacology; Titanium; Titanium - chemistry; Titanium - pharmacology; Toxic materials
• ISSN: 1742-7061; 1878-7568
• DOI: 10.1016/j.actbio.2019.03.027

[Display omitted] 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. 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.