title: Surface functionalization of titanium implants with chitosan-catechol conjugate for suppression of ROS-induced cells damage and improvement of osteogenesis.
abstract: Oxidative stress induced by reactive oxygen species (ROS) overproduction would hinder bone healing process at the interface of bone/implant, yet underlying mechanism remains to be explored. To endow titanium (Ti) substrates with antioxidant activity for enhanced bone formation, multilayered structure composing of chitosan-catechol (Chi-C), gelatin (Gel) and hydroxyapatite (HA) nanofibers was constructed on Ti substrates. Surface wettability and topography of multilayer coated Ti substrates were characterized by water contact angle measurement, scanning electron microscopy and atomic force microscopy, respectively. Chi-C containing multilayer on Ti surface effectively protected osteoblasts from ROS damage, which was revealed by high level of intracellular ROS scavenging activity and reduced oxidative damage on cellular level by regulating the expression of cell adhesion related genes (integrin αv, β3, CDH11 and CDH2). Moreover, it regulated the production of cell adhesive and anti-apoptotic related proteins (p-MYPT1, p-FAK, p-Akt and Bcl-2) and pro-apoptotic critical executioners (Bax and cleaved caspase 3). Beside, the composite multilayer of Chi-C/Gel/HA nanofibers on Ti substrates promoted osteoblasts differentiation, which was evidenced by high expression levels of alkaline phosphatase activity, collagen secretion, ECM mineralization and osteogenesis-related genes expression in vitro. The in vivo experiments of μ-CT analysis, push out test and histochemistry staining further confirmed that Chi-C multilayered implant had great potential for improved early bone healing. Overall, the study offers an effective strategy for the exploration of high quality Ti implants for orthopedic applications.
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing 400044, PR China.
authors.forename: Weizhen
authors.initials: W
authors.lastname: Chen
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing 400044, PR China.
authors.forename: Xinkun
authors.initials: X
authors.lastname: Shen
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing 400044, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing 400044, PR China.
authors.forename: Kui
authors.initials: K
authors.lastname: Xu
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing 400044, PR China.
authors.forename: Qichun
authors.initials: Q
authors.lastname: Ran
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing 400044, PR China.
authors.forename: Yonglin
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing 400044, PR China.
authors.forename: Liangliang
authors.initials: L
authors.lastname: Dai
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing 400044, PR China.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Yuan
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing 400044, PR China.
authors.forename: Ling
authors.initials: L
authors.lastname: Huang
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing 400044, PR China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Shen
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing 400044, PR China. Electronic address: kaiyong_cai@cqu.edu.cn.
authors.forename: Kaiyong
authors.initials: K
authors.lastname: Cai
mesh_terms: D000818:Animals; D002396:Catechols / Q000737:chemistry*; D002448:Cell Adhesion / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D048271:Chitosan / Q000737:chemistry*; D020099:Coated Materials, Biocompatible / Q000737:chemistry; D017886:Durapatite / Q000737:chemistry; D005260:Female; D007595:Joint Prosthesis; D058726:Nanoconjugates / Q000737:chemistry / Q000648:ultrastructure; D010006:Osteoblasts / Q000166:cytology / Q000502:physiology*; D010012:Osteogenesis / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014025:Titanium / Q000737:chemistry*
chemical_list: D002396:Catechols; D020099:Coated Materials, Biocompatible; D058726:Nanoconjugates; D017382:Reactive Oxygen Species; D048271:Chitosan; D017886:Durapatite; D014025:Titanium; C034221:catechol
keywords: Bone healing; Chitosan-catechol conjugate; Layer-by-layer assembly technique; Reactive oxygen species; Titanium