Multifunctions of dual Zn/Mg ion co-implanted titanium on osteogenesis, angiogenesis and bacteria inhibition for dental implants

• Published in: Acta biomaterialia Vol. 49; pp. 590 - 603
• Main Authors: Yu, Yiqiang, Jin, Guodong, Xue, Yang, Wang, Donghui, Liu, Xuanyong, Sun, Jiao
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-02-2017; Elsevier BV
• Subjects: Adhesive bonding; Anaerobic bacteria; Angiogenesis; Animals; Antimicrobial agents; Bacteria; Bacteria - drug effects; Bacteria, Anaerobic - drug effects; Biocompatibility; Biomechanical Phenomena - drug effects; Biomechanics; Biomedical materials; Bonding strength; Bone growth; Bone implants; Bone marrow; Bone-Implant Interface; Bone-implant interfaces; Cbfa-1 protein; Cell Adhesion - drug effects; Cell Differentiation - drug effects; Cell Proliferation - drug effects; Cell Survival - drug effects; Computed tomography; Dental implant; Dental implants; Dental Implants - microbiology; Dental materials; Dental prosthetics; Dental restorative materials; Dentures; Endothelial cells; Fluorescence; Gene expression; Human Umbilical Vein Endothelial Cells - cytology; Human Umbilical Vein Endothelial Cells - drug effects; Humans; Hypoxia; Interfaces; Ion implantation; Ions; Magnesium; Magnesium - pharmacology; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - drug effects; Mesenchyme; Multifunctions; Neovascularization, Physiologic - drug effects; Osseointegration; Osseointegration - drug effects; Osteogenesis; Osteogenesis - drug effects; Outflow; Rabbits; Rats, Sprague-Dawley; Stem cell transplantation; Stem cells; Surface Properties; Surgical implants; Titanium; Titanium - pharmacology; Titanium base alloys; Transcription; Transplants & implants; Umbilical vein; Vascular endothelial growth factor; X-Ray Microtomography; Zinc; Zinc - pharmacology; Ion implantation; Multifunctions; Magnesium; Dental implant; Zinc
• ISSN: 1742-7061; 1878-7568
• DOI: 10.1016/j.actbio.2016.11.067

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In order to improve the osseointegration and long-term survival of dental implants, it is urgent to develop a multifunctional titanium surface which would simultaneously have osteogeneic, angiogeneic and antibacterial properties. In this study, a potential dental implant material-dual Zn/Mg ion co-implanted titanium (Zn/Mg-PIII) was developed via plasma immersion ion implantation (PIII). The Zn/Mg-PIII surfaces were found to promote initial adhesion and spreading of rat bone marrow mesenchymal stem cells (rBMSCs) via the upregulation of the gene expression of integrin α1 and integrin β1. More importantly, it was revealed that Zn/Mg-PIII could increase Zn2+ and Mg2+ concentrations in rBMSCs by promoting the influx of Zn2+ and Mg2+ and inhibiting the outflow of Zn2+, and then could enhance the transcription of Runx2 and the expression of ALP and OCN. Meanwhile, Mg2+ ions from Zn/Mg-PIII increased Mg2+ influx by upregulating the expression of MagT1 transporter in human umbilical vein endothelial cells (HUVECs), and then stimulated the transcription of VEGF and KDR via activation of hypoxia inducing factor (HIF)-1α, thus inducing angiogenesis. In addition to this, it was discovered that zinc in Zn/Mg-PIII had certain inhibitory effects on oral anaerobic bacteria (Pg, Fn and Sm). Finally, the Zn/Mg-PIII implants were implanted in rabbit femurs for 4 and 12weeks with Zn-PIII, Mg-PIII and pure titanium as controls. Micro-CT evaluation, sequential fluorescent labeling, histological analysis and push-out test consistently demonstrated that Zn/Mg-PIII implants exhibit superior capacities for enhancing bone formation, angiogenesis and osseointegration, while consequently increasing the bonding strength at bone-implant interfaces. All these results suggest that due to the multiple functions co-produced by zinc and magnesium, rapid osseointegration and sustained biomechanical stability are enhanced by the novel Zn/Mg-PIII implants, which have the potential application in dental implantation in the future.
In order to enhance the rapid osseointegration and long-term survival of dental implants, various works on titanium surface modification have been carried out. However, only improving osteogenic activity of implants is not enough, because angiogenesis and bacteria inhibition are also very important for dental implants. In the present study, a novel dental implant material-dual Zn/Mg ion co-implanted titanium (Zn/Mg-PIII) was developed, which was found to have superior osteoinductivity, pro-angiogenic effects and inhibitory effects against oral anaerobes. Furthermore, synergistic effects of Zn/Mg ions on osteogenic differentiation of rBMSCs and the possible mechanism were discovered. In addition, rapid osseointegration and sustained biomechanical stability are greatly enhanced by Zn/Mg-PIII implants, which may have the potential application in dental implantation in the future. We believe this paper may be of particular interest to the readers.