title: The promotion of osteointegration under diabetic conditions using chitosan/hydroxyapatite composite coating on porous titanium surfaces.
abstract: Composited Chitosan/Hydroxyapatite (CS/HA) material coated on titanium surface (cTi) is a promising approach to produce biomaterials with better osseointegration capacity, but its bio-performance under diabetic conditions and the mechanisms involved remain elusive. We propose that the alterations in the Wnt/β-catenin pathway may play a role in mediating the improvement effect of cTi on diabetes-induced impaired implant osteointegration. To confirm the hypothesis, primary rat osteoblasts incubated on Ti and cTi were subjected to normal serum (NS), diabetic serum (DS), DS + Wnt3a (a specific Wnt agonist) and DS + Dkk1 (a specific Wnt antagonist) treatment. In vivo study was performed on diabetic sheep implanted with Ti or cTi into the bone defect on crista iliaca. Results showed that diabetes depressed osteoblast function evidenced by impaired cell adhesion and morphology, decreased cell proliferation and ALP activity, and higher apoptotic rate on Ti. Importantly, both cTi and Wnt3a treatment ameliorated osteoblastic dysfunction and apoptosis under diabetic condition. Implantation with cTi significantly improved osteointegration evidenced by Micro-CT and histological examinations compared with Ti. Moreover, the aforementioned promotive effects afforded by cTi were abolished by blocking Wnt pathway with Dkk1. Our study explicitly demonstrates that CS/HA composite material improves diabetes-induced impaired osteointegration of Ti via the reactivation of Wnt/β-catenin pathway and provides a target point for biomaterial modification to attain better clinical performance in diabetic patients.
authors.affiliation: Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, People's Republic of China.
authors.forename: Xiang-Yu
authors.initials: XY
authors.lastname: Ma
authors.affiliation: Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, People's Republic of China.
authors.forename: Ya-Fei
authors.initials: YF
authors.lastname: Feng
authors.affiliation: Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, People's Republic of China.
authors.forename: Zhen-Sheng
authors.initials: ZS
authors.lastname: Ma
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, Fourth Military Medical University, Xi'an, Shaanxi 710032, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, People's Republic of China. Electronic address: wanglinxj@fmmu.edu.cn.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, People's Republic of China. Electronic address: leiwei@fmmu.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Lei
mesh_terms: D000818:Animals; D018786:Bone Substitutes / Q000737:chemistry* / Q000378:metabolism; D002470:Cell Survival; D002478:Cells, Cultured; D048271:Chitosan / Q000737:chemistry* / Q000378:metabolism; D020099:Coated Materials, Biocompatible / Q000737:chemistry* / Q000378:metabolism; D048909:Diabetes Complications / Q000150:complications* / Q000378:metabolism; D017886:Durapatite / Q000737:chemistry* / Q000378:metabolism; D008297:Male; D016348:Osseointegration; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D016062:Porosity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012756:Sheep; D054457:Tissue Scaffolds / Q000737:chemistry; D014025:Titanium / Q000737:chemistry* / Q000378:metabolism; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism
chemical_list: D018786:Bone Substitutes; D020099:Coated Materials, Biocompatible; D051176:beta Catenin; D048271:Chitosan; D017886:Durapatite; D014025:Titanium
keywords: Chitosan; Diabetes; Hydroxyapatite; Porous titanium; Wnt/β-catenin