title: Improved implant osseointegration of a nanostructured titanium surface via mediation of macrophage polarization.
abstract: The use of endosseous implanted materials is often limited by undesirable effects that may be due to macrophage-related inflammation. The purpose of this study was to fabricate a nanostructured surface on a titanium implant to regulate the macrophage inflammatory response and improve the performance of the implant. Anodization at 5 and 20 V as well as UV irradiation were used to generate hydrophilic, nanostructured TiO2 surfaces (denoted as NT5 and NT20, respectively). Their surface characteristics and in vivo osseointegration as well as the inflammatory response they elicit were analyzed. In addition, the behavior of macrophages in vitro was evaluated. Although the in vitro osteogenic activity on the two surfaces was similar, the NT5 surface was associated with more bone formation, less inflammation, and a reduced CD68(+) macrophage distribution in vivo compared to the NT20 and polished Ti surfaces. Consistently, further experiments revealed that the NT5 surface induced healing-associated M2 polarization in vitro and in vivo. By contrast, the NT20 surface promoted the pro-inflammatory M1 polarization, which could further impair bone regeneration. The results demonstrate the dominant role of macrophage-related inflammation in bone healing around implants and that surface nanotopography can be designed to have an immune-regulating effect in support of the success of implants.
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Prosthetic Dentistry, School of Stomatology, Fourth Military Medical University, Xi'an, China.
authors.forename: Qian-Li
authors.initials: QL
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Periodontology, School of Stomatology, Fourth Military Medical University, Xi'an, China.
authors.forename: Ling-Zhou
authors.initials: LZ
authors.lastname: Zhao
authors.affiliation: Department of Immunology, School of Basic Medicine, Fourth Military Medical University, Xi'an, China.
authors.forename: Rong-Rong
authors.initials: RR
authors.lastname: Liu
authors.affiliation: Department of Immunology, School of Basic Medicine, Fourth Military Medical University, Xi'an, China.
authors.forename: Bo-Quan
authors.initials: BQ
authors.lastname: Jin
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Prosthetic Dentistry, School of Stomatology, Fourth Military Medical University, Xi'an, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Song
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Periodontology, School of Stomatology, Fourth Military Medical University, Xi'an, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Immunology, School of Basic Medicine, Fourth Military Medical University, Xi'an, China.
authors.forename: Yu-Si
authors.initials: YS
authors.lastname: Zhang
authors.affiliation: Department of Immunology, School of Basic Medicine, Fourth Military Medical University, Xi'an, China. Electronic address: Chenlh@fmmu.edu.cn.
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Prosthetic Dentistry, School of Stomatology, Fourth Military Medical University, Xi'an, China. Electronic address: wqtzym@fmmu.edu.cn.
authors.forename: Yu-Mei
authors.initials: YM
authors.lastname: Zhang
mesh_terms: D000818:Animals; D018786:Bone Substitutes / Q000737:chemistry* / Q000378:metabolism; D002478:Cells, Cultured; D020099:Coated Materials, Biocompatible / Q000737:chemistry / Q000378:metabolism; D005269:Femur / Q000293:injuries / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000209:etiology* / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D008297:Male; D049329:Nanostructures / Q000737:chemistry*; D016348:Osseointegration; D019736:Prostheses and Implants / Q000009:adverse effects*; D017207:Rats, Sprague-Dawley; D013499:Surface Properties; D014025:Titanium / Q000737:chemistry* / Q000276:immunology
chemical_list: D018786:Bone Substitutes; D020099:Coated Materials, Biocompatible; D014025:Titanium
keywords: Implant; Inflammation; Macrophage polarization; Surface nanotopography