title: Nano-layered magnesium fluoride reservoirs on biomaterial surfaces strengthen polymorphonuclear leukocyte resistance to bacterial pathogens.
abstract: Biomaterial-related bacterial infections cause patient suffering, mortality and extended periods of hospitalization, imposing a substantial burden on medical systems. In this context, understanding of nanomaterials-bacteria-cells interactions is of both fundamental and clinical significance. Herein, nano-MgF2films were deposited on titanium substrate via magnetron sputtering. Using this platform, the antibacterial behavior and mechanism of the nano-MgF2films were investigated in vitro and in vivo. It was found that, for S. aureus (CA-MRSA, USA300) and S. epidermidis (RP62A), the nano-MgF2films possessed excellent anti-biofilm activity, but poor anti-planktonic bacteria activity in vitro. Nevertheless, both the traditional SD rat osteomyelitis model and the novel stably luminescent mouse infection model demonstrated that nano-MgF2films exerted superior anti-infection effect in vivo, which cannot be completely explained by the antibacterial activity of the nanomaterial itself. Further, using polymorphonuclear leukocytes (PMNs), the critical immune cells of innate immunity, a complementary investigation of MgF2-bacteria-PMNs co-culturing revealed that the nano-MgF2films improved the antibacterial effect of PMNs through enhancing their phagocytosis and stability. To our knowledge, this is the first time of exploring the antimicrobial mechanism of nano-MgF2from the perspective of innate immunity both in vitro and in vivo. Based on the research results, a plausible mechanism is put forward for the predominant antibacterial effect of nano-MgF2in vivo, which may originate from the indirect immune enhancement effect of nano-MgF2films. In summary, this study of surface antibacterial design using MgF2nanolayer is a meaningful attempt, which can promote the host innate immune response to bacterial pathogens. This may give us a new understanding towards the antibacterial behavior and mechanism of nano-MgF2films and pave the way towards their clinical applications.
authors.affiliation: Department of Orthopaedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai 200233, China. shenhao7212@sina.com.
authors.forename: Geyong
authors.initials: G
authors.lastname: Guo
authors.affiliation: State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, China. p-jin@mail.sic.ac.cn lijinhua429@gmail.com.
authors.forename: Huaijuan
authors.identifier: http://orcid.org/0000-0002-9289-3613
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Orthopaedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai 200233, China. shenhao7212@sina.com.
authors.forename: Qiaojie
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Orthopaedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai 200233, China. shenhao7212@sina.com.
authors.forename: Jiaxing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Orthopaedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai 200233, China. shenhao7212@sina.com.
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Tan
authors.affiliation: State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, China. p-jin@mail.sic.ac.cn lijinhua429@gmail.com and University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Jinhua
authors.identifier: http://orcid.org/0000-0003-1110-7471
authors.initials: J
authors.lastname: Li
authors.affiliation: State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, China. p-jin@mail.sic.ac.cn lijinhua429@gmail.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Jin
authors.affiliation: Department of Orthopaedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai 200233, China. shenhao7212@sina.com.
authors.forename: Hao
authors.identifier: http://orcid.org/0000-0002-8698-5079
authors.initials: H
authors.lastname: Shen
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents; D001672:Biocompatible Materials; D018441:Biofilms / Q000187:drug effects; D002478:Cells, Cultured; D005459:Fluorides / Q000737:chemistry*; D006801:Humans; D017616:Magnesium Compounds / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D049329:Nanostructures / Q000737:chemistry*; D009504:Neutrophils / Q000276:immunology / Q000382:microbiology*; D010019:Osteomyelitis / Q000628:therapy; D010587:Phagocytosis; D016459:Prosthesis-Related Infections / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley; D013203:Staphylococcal Infections / Q000517:prevention & control*; D013211:Staphylococcus aureus
chemical_list: D000900:Anti-Bacterial Agents; D001672:Biocompatible Materials; D017616:Magnesium Compounds; C031288:magnesium fluoride; D005459:Fluorides