title: Promotion of osteointegration under diabetic conditions by tantalum coating-based surface modification on 3-dimensional printed porous titanium implants.
abstract: Clinical evidence indicates a high failure rate for titanium implants (TiI) in diabetic patients, involving the overproduction of reactive oxygen species (ROS) at the implant/bone interface. Tantalum coating on titanium (TaTi) has exerted better tissue integration properties than TiI, but its biological performance under diabetic conditions remains elusive. To investigate whether TaTi may ameliorate diabetes-induced implant destabilization and the underlying mechanisms, primary rabbit osteoblasts cultured on 3-dimensional printed TiI and TaTi were exposed to normal serum (NS), diabetic serum (DS), DS+NAC (a potent ROS inhibitor), and DS+SB203580 (a specific p38 MAPK inhibitor). An in vivo study was performed on diabetic sheep implanted with TiI or TaTi. Diabetes induced mitochondrial-derived ROS overproduction and caused cellular dysfunction and apoptosis, together with the activation of p38 MAPK in osteoblasts on TiI surface. Importantly, TaTi significantly attenuated ROS production and p38 MAPK phosphorylation and exerted more osseointegrative cell behavior than TiI, as shown by improved osteoblast adhesion, increased cell proliferation and differentiation and decreased apoptosis. These results were confirmed in vivo by the enhanced bone healing efficacy of TaTi. Moreover, treatment with NAC or SB203580 on TiI not only inhibited the activation of p38 MAPK but also improved cell function and alleviated apoptotic injury, whereas TaTi combined with NAC or SB203580 failed to further improve osteoblast functional recovery compared with TaTi alone. These results demonstrated that the tantalum coating markedly improved diabetes-induced impaired osteogenesis of TiI, which may be attributed to the suppression of the ROS-mediated p38 MAPK pathway.
authors.affiliation: Department of Orthopedics, Xijing Hospital, The Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, Xijing Hospital, The Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
authors.forename: Xiaofan
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Orthopedics, Xijing Hospital, The Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Ma
authors.affiliation: Department of Orthopedics, Xijing Hospital, The Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
authors.forename: Zhensheng
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Department of Orthopedics, Xijing Hospital, The Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics, Xijing Hospital, The Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
authors.forename: Yizhao
authors.initials: Y
authors.lastname: Lu
authors.affiliation: School of Mechanical Engineering, Shanghai Jiao Tong University, State Key Laboratory of Mechanical System and Vibration, Shanghai, 200240, People's Republic of China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Orthopedics, Xijing Hospital, The Fourth Military Medical University, Xi'an, 710032, People's Republic of China. Electronic address: leiwei@fmmu.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Lei
authors.affiliation: Department of Orthopedics, Xijing Hospital, The Fourth Military Medical University, Xi'an, 710032, People's Republic of China. Electronic address: fengyafei2005@163.com.
authors.forename: Yafei
authors.initials: Y
authors.lastname: Feng
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D020099:Coated Materials, Biocompatible / Q000737:chemistry*; D003920:Diabetes Mellitus / Q000097:blood / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology; D008855:Microscopy, Electron, Scanning; D016348:Osseointegration / Q000502:physiology*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016062:Porosity; D066330:Printing, Three-Dimensional; D019736:Prostheses and Implants; D011725:Pyridines / Q000494:pharmacology; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism; D044967:Serum / Q000737:chemistry; D012756:Sheep; D013499:Surface Properties; D013635:Tantalum / Q000737:chemistry*; D014025:Titanium / Q000737:chemistry*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D020099:Coated Materials, Biocompatible; D007093:Imidazoles; D011725:Pyridines; D017382:Reactive Oxygen Species; D013635:Tantalum; D014025:Titanium; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580
keywords: Diabetes; Interface; MAPK; Porous titanium; ROS; Tantalum coating