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Journal of Orthopaedic Surgery and Research
Published in: Journal of Orthopaedic Surgery and Research 1/2017

Open Access 01-12-2017 | Research article

Reducing the risk of impaired bone apposition to titanium screws with the use of fibroblast growth factor-2−apatite composite layer coating

Authors: Kengo Fujii, Atsuo Ito, Hirotaka Mutsuzaki, Shinji Murai, Yu Sogo, Yuki Hara, Masashi Yamazaki

Published in: Journal of Orthopaedic Surgery and Research | Issue 1/2017

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Abstract

Background

Loosening of screws is a common problem in orthopedic and maxillofacial surgery. Modifying the implant surface to improve the mechanical strength of screws has been tried and reported. We developed screws coated with fibroblast growth factor-2 (FGF-2)−apatite composite layers. We then showed, in a percutaneous external fixation model, that this composite layer had the ability to hold and release FGF-2 slowly, thereby reducing the risk of pin tract infection of the percutaneous external fixation. The objective of the current study was to clarify the effect of FGF-2−apatite composite layers on titanium screws on bone formation around the screw.

Methods

We analyzed samples of previously performed animal experiments. The screws were coated with FGF-2−apatite composite layers by immersing them in supersaturated calcium phosphate solutions containing FGF-2. Then, the uncoated, apatite-coated, and FGF-2−apatite composite layer-coated screws were implanted percutaneously in rabbits. Finally, using inflammation-free histological sections, we histomorphometrically assessed them for the presence of bone formation. Weibull plot analysis was then applied to the data.

Results

On average, screws coated with FGF-2−apatite composite layers showed a significantly higher bone apposition rate than the uncoated or apatite-coated screws. Although the difference in the average bone apposition rate was small, the FGF-2−apatite composite layers produced a significant, marked reduction in the incidence of impaired bone formation around the screw compared with the incidence in the absence of FGF-2 (uncoated and apatite-coated screws). The probability of resulting in a bone apposition rate equal to or less than 63.75%, for example, is 3.5 × 10-4 for screws coated with the FGF-2−apatite composite layers versus 0.05 for screws in the absence of FGF-2.

Conclusions

FGF-2-apatite composite layer coating significantly reduced the risk of impaired bone apposition to the screw. Thus, it is feasible to use titanium screws coated with FGF-2−apatite composite layers as internal fixation screws to decrease the risk of loosening.
Literature
1.
Galbusera F, Volkheimer D, Reitmaier S, Berger-Roscher N, Kienle A, Wilke HJ. Pedicle screw loosening: a clinically relevant complication? Eur Spine J. 2015;24:1005–16.CrossRefPubMed
2.
Wu JC, Huang WC, Tsai HW, Ko CC, Wu CL, Tu TH, et al. Pedicle screw loosening in dynamic stabilization: incidence, risk, and outcome in 126 patients. Neurosurg Focus. 2011;31:E9.CrossRefPubMed
3.
Kocak T, Cakir B, Reichel H, Mattes T. Screw loosening after posterior dynamic stabilization: review of the literature. Acta Chir Orthop Traumatol Cech. 2010;77:134–9.PubMed
4.
Shea TM, Laun J, Gonzalez-Blohm SA, Doulgeris JJ, Lee 3rd WE, Aghayev K, et al. Designs and techniques that improve the pullout strength of pedicle screws in osteoporotic vertebrae: current status. Biomed Res Int. 2014;2014:748393.CrossRefPubMedPubMedCentral
5.
Hasegawa T, Inufusa A, Imai Y, Mikawa Y, Lim TH, An HS. Hydroxyapatite-coating of pedicle screws improves resistance against pull-out force in the osteoporotic canine lumbar spine model: a pilot study. Spine J. 2005;5:239–43.CrossRefPubMed
6.
Surmenev RA, Surmeneva MA, Ivanova AA. Significance of calcium phosphate coatings for the enhancement of new bone osteogenesis: a review. Acta Biomater. 2014;10:557–79.CrossRefPubMed
7.
8.
Qiu ZY, Chen C, Wang XM, Lee IS. Advances in the surface modification techniques of bone-related implants for last 10 years. Regen Biomater. 2014;1:67–79.CrossRefPubMedPubMedCentral
9.
Raj V, Raj RM, Sasireka A, Priya P. Fabrication of TiO2-strontium loaded CaSiO3/biopolymer coatings with enhanced biocompatibility and corrosion resistance by controlled release of minerals for improved orthopedic applications. J Mech Behav Biomed Mater. 2016;60:476–91.CrossRefPubMed
10.
Yu J, Li K, Zheng X, He D, Ye X, Wang M. In vitro and in vivo evaluation of zinc-modified Ca-Si-based ceramic coating for bone implants. PLoS One. 2013;8:e57564.CrossRefPubMedPubMedCentral
11.
Mueller CK, Thorwarth M, Schmidt M, Schlegel KA, Schultze-Mosgau S. Comparative analysis of osseointegration of titanium implants with acid-etched surfaces and different biomolecular coatings. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2011;112:726–36.CrossRefPubMed
12.
Wu C, Ramaswamy Y, Liu X, Wang G, Zreiqat H. Plasma-sprayed CaTiSiO5 ceramic coating on Ti-6Al-4V with excellent bonding strength, stability and cellular bioactivity. J R Soc Interface. 2009;6:159–68.CrossRefPubMed
13.
Sogo Y, Ito A, Onoguchi M, Oyane A, Tsurushima H, Ichinose N. Formation of a FGF-2 and calcium phosphate composite layer on a hydroxyapatite ceramic for promoting bone formation. Biomed Mater. 2007;2:S175–80.CrossRefPubMed
14.
15.
Lee SW, Hahn BD, Kang TY, Lee MJ, Choi JY, Kim MK, et al. Hydroxyapatite and collagen combination-coated dental implants display better bone formation in the peri-implant area than the same combination plus bone morphogenetic protein-2-coated implants, hydroxyapatite only coated implants, and uncoated implants. J Oral Maxillofac Surg. 2014;72:53–60.CrossRefPubMed
16.
Lee JS, Yang JH, Hong JY, Jung UW, Yang HC, Lee IS, et al. Early bone healing onto implant surface treated by fibronectin/oxysterol for cell adhesion/osteogenic differentiation: in vivo experimental study in dogs. J Periodontal Implant Sci. 2014;44:242–50.CrossRefPubMedPubMedCentral
17.
Naito Y, Jimbo R, Bryington MS, Vandeweghe S, Chrcanovic BR, Tovar N, et al. The influence of 1α.25-dihydroxyvitamin d3 coating on implant osseointegration in the rabbit tibia. J Oral Maxillofac Res. 2014;5:e3.PubMedPubMedCentral
18.
Fang K, Song W, Wang L, Jia S, Wei H, Ren S, et al. Immobilization of chitosan film containing semaphorin 3A onto a microarc oxidized titanium implant surface via silane reaction to improve MG63 osteogenic differentiation. Int J Nanomedicine. 2014;9:4649–57.PubMedPubMedCentral
19.
Niu S, Cao X, Zhang Y, Zhu Q, Zhu J. The inhibitory effect of alendronate-hydroxyapatite composite coating on wear debris-induced peri-implant high bone turnover. J Surg Res. 2013;179:e107–15.CrossRefPubMed
20.
Kim SE, Suh DH, Yun YP, Lee JY, Park K, Chung JY, et al. Local delivery of alendronate eluting chitosan scaffold can effectively increase osteoblast functions and inhibit osteoclast differentiation. J Mater Sci Mater Med. 2012;23:2739–49.CrossRefPubMed
21.
Wang JS, Aspenberg P. Basic fibroblast growth factor promotes bone ingrowth in porous hydroxyapatite. Clin Orthop Relat Res. 1996;333:252–60.CrossRef
22.
Liu Y, Cai S, Shu XZ, Shelby J, Prestwich GD. Release of basic fibroblast growth factor from a crosslinked glycosaminoglycan hydrogel promotes wound healing. Wound Repair Regen. 2007;15:245–51.CrossRefPubMed
23.
Tsurushima H, Marushima A, Suzuki K, Oyane A, Sogo Y, Nakamura K, et al. Enhanced bone formation using hydroxyapatite ceramic coated with fibroblast growth factor-2. Acta Biomater. 2010;6:2751–9.CrossRefPubMed
24.
Mutsuzaki H, Ito A, Sogo Y, Sakane M, Oyane A, Yamazaki M. The calcium phosphate matrix of FGF-2-apatite composite layers contributes to their biological effects. Int J Mol Sci. 2014;15:10252–70.CrossRefPubMedPubMedCentral
25.
Mutsuzaki H, Ito A, Sakane M, Sogo Y, Oyane A, Ochiai N. Fibroblast growth factor-2-apatite composite layers on titanium screw to reduce pin tract infection rate. J Biomed Mater Res B Appl Biomater. 2008;86:365–74.CrossRefPubMed
26.
Wang X, Ito A, Sogo Y, Li X, Tsurushima H, Oyane A. Ascorbate-apatite composite and ascorbate-FGF-2-apatite composite layers formed on external fixation rods and their effects on cell activity in vitro. Acta Biomater. 2009;5:2647–56.CrossRefPubMed
27.
Weibull W. A statistical distribution function of wide applicability. J Applied Mechanics. 1951;8:293–7.
28.
Mutsuzaki H, Ito A, Sogo Y, Sakane M, Oyane A, Ochiai N. Enhanced wound healing associated with Sharpey’s fiber-like tissue formation around FGF-2-apatite composite layers on percutaneous titanium screws in rabbits. Arch Orthop Trauma Surg. 2012;132:113–21.CrossRefPubMed
29.
Mutsuzaki H, Sogo Y, Oyane A, Ito A. Improved bonding of partially osteomyelitic bone to titanium pins owing to biomimetic coating of apatite. Int J Mol Sci. 2013;14:24366–79.CrossRefPubMedPubMedCentral
30.
Wittenberg RH, Shea M, Swartz DE, Lee KS, White 3rd AA, Hayes WC. Importance of bone mineral density in instrumented spine fusions. Spine (Phila Pa 1976). 1991;16:647–52.CrossRef
31.
Halvorson TL, Kelley LA, Thomas KA, Whitecloud 3rd TS, Cook SD. Effects of bone mineral density on pedicle screw fixation. Spine (Phila Pa 1976). 1994;19:2415–20.CrossRef
32.
Inoue G, Ueno M, Nakazawa T, Imura T, Saito W, Uchida K, et al. Teriparatide increases the insertional torque of pedicle screws during fusion surgery in patients with postmenopausal osteoporosis. J Neurosurg Spine. 2014;21:425–31.CrossRefPubMed
33.
Sandén B, Olerud C, Petrén-Mallmin M, Johansson C, Larsson S. The significance of radiolucent zones surrounding pedicle screws: definition of screw loosening in spinal instrumentation. J Bone Joint Surg (Br). 2004;86:457–61.CrossRef
34.
Upasani VV, Farnsworth CL, Tomlinson T, Chambers RC, Tsutsui S, Slivka MA, et al. Pedicle screw surface coatings improve fixation in nonfusion spinal constructs. Spine (Phila Pa 1976). 2009;34:335–43.CrossRef
35.
Nagayasu-Tanaka T, Nozaki T, Miki K, Sawada K, Kitamura M, Murakami S. FGF-2 promotes initial osseointegration and enhances stability of implants with low primary stability. Clin Oral Impl Res. 2016. doi:10.​1111/​clr.​12797 [Epub ahead of print].
36.
Gao Y, Luo E, Hu J, Xue J, Zhu S, Li J. Effect of combined local treatment with zoledronic acid and basic fibroblast growth factor on implant fixation in ovariectomized rats. Bone. 2009;44:225–32.CrossRefPubMed
37.
Honnami M, Choi S, Liu IL, Kamimura W, Taguchi T, Hojo H, et al. Repair of rabbit segmental femoral defects by using a combination of tetrapod-shaped calcium phosphate granules and basic fibroblast growth factor-binding ion complex gel. Biomaterials. 2013;34:9056–62.CrossRefPubMed
38.
Luong LN, Ramaswamy J, Kohn DH. Effects of osteogenic growth factors on bone marrow stromal cell differentiation in a mineral-based delivery system. Biomaterials. 2012;33:283–94.CrossRefPubMed
39.
Nakajima F, Nakajima A, Ogasawara A, Moriya H, Yamazaki M. Effects of a single percutaneous injection of basic fibroblast growth factor on the healing of a closed femoral shaft fracture in the rat. Calcif Tissue Int. 2007;81:132–8.CrossRefPubMed
40.
Behr B, Sorkin M, Lehnhardt M, Renda A, Longaker MT, Quarto N. A comparative analysis of the osteogenic effects of BMP-2, FGF-2, and VEGFA in a calvarial defect model. Tissue Eng Part A. 2012;18:1079–86.CrossRefPubMedPubMedCentral
Metadata
Title
Reducing the risk of impaired bone apposition to titanium screws with the use of fibroblast growth factor-2−apatite composite layer coating
Authors
Kengo Fujii
Atsuo Ito
Hirotaka Mutsuzaki
Shinji Murai
Yu Sogo
Yuki Hara
Masashi Yamazaki
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Journal of Orthopaedic Surgery and Research / Issue 1/2017
Electronic ISSN: 1749-799X
DOI
https://doi.org/10.1186/s13018-016-0501-z

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