title: Enhancement of local bone remodeling in osteoporotic rabbits by biomimic multilayered structures on Ti6Al4V implants.
abstract: To enhance long-term survival of titanium implants in patients with osteoporosis, chitosan/gelatin multilayers containing bone morphogenetic protein 2(BMP2) and an antiosteoporotic agent of calcitonin (CT) are deposited on the Ti6Al4V (TC4) implants through layer-by-layer (LBL) electrostatic assembly technique. Here, the obtained titanium alloy implant (TC4/LBL/CT/BMP2) can regulate the release of loaded calcitonin and BMP2 agents in a sustaining manner to accelerate the bone formation and simultaneously inhibit bone resorption. In vitro results show that the bone-related cells on TC4/LBL/CT/BMP2 present the lowest production level of tartrate resistant acid phosphatase (TRAP) but the highest (p < 0.05) level of alkaline phosphatase (ALP) activity, osteocalcin production, mineralization capacity and osteoblast-related gene expression among all groups after treatment for 7 or 21 days, respectively. Besides, in vivo studies of micro-CT analysis, routine histological and immunohistochemical analysis also collectively demonstrate that the TC4/LBL/CT/BMP2 implant can dramatically promote the formation and remodeling of new bone in osteoporotic rabbits after implantation for 30 days and 90 days, respectively. In vivo push-out testing further confirms that the TC4/LBL/CT/BMP2 implant has the highest (p < 0.01) interfacial shear strength and favorable bone-implant osseointegration. Overall, this study establishes a simple and profound methodology to fabricate a biofunctional TC4 implant for the treatment of local osteoporotic fractures in vivo. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1437-1451, 2016.
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, 400044, People's Republic of China.
authors.forename: Ling
authors.initials: L
authors.lastname: Huang
authors.affiliation: School of Life Science, Chongqing University, Chongqing, 400044, People's Republic of China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Luo
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, 400044, People's Republic of 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, People's Republic of China.
authors.forename: Xinkun
authors.initials: X
authors.lastname: Shen
authors.affiliation: School of Life Science, Chongqing University, Chongqing, 400044, People's Republic of China.
authors.forename: Menghuan
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Xinqiao Street, Chongqing, 400037, People's Republic of China.
authors.forename: Liqi
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Xinqiao Street, Chongqing, 400037, People's Republic of China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, 400044, People's Republic of China.
authors.forename: Weihu
authors.initials: W
authors.lastname: Yang
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, 400044, People's Republic of China.
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, 400044, People's Republic of China.
authors.forename: Kaiyong
authors.initials: K
authors.lastname: Cai
mesh_terms: D000497:Alloys; D000818:Animals; D001119:Arginase / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D040761:Biomimetic Materials / Q000494:pharmacology*; D016723:Bone Remodeling / Q000187:drug effects*; D000069343:Bone-Implant Interface; D002454:Cell Differentiation / Q000187:drug effects; D065546:Drug Liberation; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D020007:Implants, Experimental; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects; D051379:Mice; D016348:Osseointegration / Q000187:drug effects; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics; D010024:Osteoporosis / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology*; D000067996:RAW 264.7 Cells; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D014025:Titanium / Q000494:pharmacology*
chemical_list: D000497:Alloys; D015415:Biomarkers; D012333:RNA, Messenger; C031462:titanium alloy (TiAl6V4); D014025:Titanium; D001119:Arginase
keywords: BMP2; Ti6Al4V implants; calcitonin; layer-by-layer assembly technique; osteoporosis