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Published in: Archives of Orthopaedic and Trauma Surgery 1/2012

01-01-2012 | Basic Science

Enhanced wound healing associated with Sharpey’s fiber-like tissue formation around FGF-2-apatite composite layers on percutaneous titanium screws in rabbits

Authors: Hirotaka Mutsuzaki, Atsuo Ito, Yu Sogo, Masataka Sakane, Ayako Oyane, Naoyuki Ochiai

Published in: Archives of Orthopaedic and Trauma Surgery | Issue 1/2012

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Abstract

Background

Pin-tract infections are the most common complications of external fixation. To solve the problem, we developed a fibroblast growth factor-2 (FGF-2)-apatite composite layer for coating titanium screws. The purpose of this study was to elucidate the mechanism of the improvement in infection resistance associated with FGF-2-apatite composite layers.

Method

We analyzed FGF-2 release from the FGF-2-apatite composite layer and the mitogenic activity of the FGF-2-apatite composite layer. We evaluated time-dependent development of macroscopic pin-tract infection around uncoated titanium control screws (n = 10). Screws coated with the apatite layer (n = 16) and FGF-2-apatite composite layer (n = 16) were percutaneously implanted for 4 weeks in the medial proximal tibia in rabbits.

Results

A FGF-2-apatite composite layer coated on the screws led to the retention of the mitogenic activity of FGF-2. FGF-2 was released from the FGF-2-apatite composite layer in vitro for at least 4 days, which corresponds to a period when 30% of pin-tract infections develop macroscopically in the percutaneous implantation of uncoated titanium control screws. The macroscopic infection rate increased with time, reaching a plateau of 80–90% within 12 days. This value remained unchanged until 4 weeks after implantation. The screws coated with an FGF-2-apatite composite layer showed a significantly higher wound healing rate than those coated with an apatite layer (31.25 vs. 6.25%, p < 0.05). The interfacial soft tissue that bonded to the FGF-2-apatite composite layer is a Sharpey’s fiber-like tissue, where collagen fibers are inclined at angles from 30 to 40° to the screw surface. The Sharpey’s Wber-like tissue is rich in blood vessels and directly bonds to the FGF-2-apatite composite layer via a thin cell monolayer (0.8–1.7 μm thick).

Conclusion

It is suggested that the enhanced wound healing associated with the formation of Sharpey’s fiber-like tissue triggered by FGF-2 released from the FGF-2-apatite composite layer leads to the reduction in the pin-tract inflammation rate.
Literature
1.
go back to reference Oh CW, Kim SJ, Park SK, Kim HJ, Kyung HS, Cho HS, Park BC, Ihn JC (2011) Hemicallotasis for correction of varus deformity of the proximal tibia using a unilateral external fixator. J Orthop Sci 16:44–50PubMedCrossRef Oh CW, Kim SJ, Park SK, Kim HJ, Kyung HS, Cho HS, Park BC, Ihn JC (2011) Hemicallotasis for correction of varus deformity of the proximal tibia using a unilateral external fixator. J Orthop Sci 16:44–50PubMedCrossRef
2.
go back to reference Catagni MA, Lovisetti L, Guerreschi F, Camagni M, Albisetti W, Compagnoni P, Combi A (2010) The external fixation in the treatment of humeral diaphyseal fractures: outcomes of 84 cases. Injury 41:1107–1111PubMedCrossRef Catagni MA, Lovisetti L, Guerreschi F, Camagni M, Albisetti W, Compagnoni P, Combi A (2010) The external fixation in the treatment of humeral diaphyseal fractures: outcomes of 84 cases. Injury 41:1107–1111PubMedCrossRef
3.
go back to reference Lamm BM, Gottlieb HD, Paley D (2010) A two-stage percutaneous approach to charcot diabetic foot reconstruction. J Foot Ankle Surg 49:517–522PubMedCrossRef Lamm BM, Gottlieb HD, Paley D (2010) A two-stage percutaneous approach to charcot diabetic foot reconstruction. J Foot Ankle Surg 49:517–522PubMedCrossRef
4.
go back to reference Pieske O, Geleng P, Zaspel J, Piltz S (2008) Titanium alloy pins versus stainless steel pins in external fixation at the wrist: a randomized prospective study. J Trauma 64:1275–1280PubMedCrossRef Pieske O, Geleng P, Zaspel J, Piltz S (2008) Titanium alloy pins versus stainless steel pins in external fixation at the wrist: a randomized prospective study. J Trauma 64:1275–1280PubMedCrossRef
5.
go back to reference Cavusoglu AT, Er MS, Inal S, Ozsoy MH, Dincel VE, Sakaogullari A (2009) Pin site care during circular external fixation using two different protocols. J Orthop Trauma 23:724–730PubMedCrossRef Cavusoglu AT, Er MS, Inal S, Ozsoy MH, Dincel VE, Sakaogullari A (2009) Pin site care during circular external fixation using two different protocols. J Orthop Trauma 23:724–730PubMedCrossRef
6.
go back to reference Savolainen VT, Pajarinen J, Hirvensalo E, Lindahl J (2010) Hybrid external fixation in treatment of proximal tibial fractures: a good outcome in AO/ASIF type-C fractures. Arch Orthop Trauma Surg 130:897–901PubMedCrossRef Savolainen VT, Pajarinen J, Hirvensalo E, Lindahl J (2010) Hybrid external fixation in treatment of proximal tibial fractures: a good outcome in AO/ASIF type-C fractures. Arch Orthop Trauma Surg 130:897–901PubMedCrossRef
7.
go back to reference Mutsuzaki H, Ito A, Sakane M, Sogo Y, Oyane A, Ochiai N (2008) FGF-2-apatite composite layers on titanium screws to reduce pin tract infection rate. J Biomed Mater Res B 86:365–374 Mutsuzaki H, Ito A, Sakane M, Sogo Y, Oyane A, Ochiai N (2008) FGF-2-apatite composite layers on titanium screws to reduce pin tract infection rate. J Biomed Mater Res B 86:365–374
8.
go back to reference Mutsuzaki H, Ito A, Sakane M, Sogo Y, Oyane A, Ebihara Y, Ichinose N, Ochiai N (2007) Calcium phosphate coating formed in infusion fluid mixture to enhance fixation strength of titanium screws. J Mater Sci Mater Med 18:1799–1808PubMedCrossRef Mutsuzaki H, Ito A, Sakane M, Sogo Y, Oyane A, Ebihara Y, Ichinose N, Ochiai N (2007) Calcium phosphate coating formed in infusion fluid mixture to enhance fixation strength of titanium screws. J Mater Sci Mater Med 18:1799–1808PubMedCrossRef
9.
go back to reference Bhang SH, Sun AY, Yang HS, Rhim T, Kim DI, Kim BS (2011) Skin regeneration with fibroblast growth factor 2 released from heparin-conjugated fibrin. Biotechnol Lett 33:845–851PubMedCrossRef Bhang SH, Sun AY, Yang HS, Rhim T, Kim DI, Kim BS (2011) Skin regeneration with fibroblast growth factor 2 released from heparin-conjugated fibrin. Biotechnol Lett 33:845–851PubMedCrossRef
10.
go back to reference Shi C, Chen W, Zhao Y, Chen B, Xiao Z, Wei Z, Hou X, Tang J, Wang Z, Dai J (2011) Regeneration of full-thickness abdominal wall defects in rats using collagen scaffolds loaded with collagen-binding basic fibroblast growth factor. Biomaterials 32:753–759PubMedCrossRef Shi C, Chen W, Zhao Y, Chen B, Xiao Z, Wei Z, Hou X, Tang J, Wang Z, Dai J (2011) Regeneration of full-thickness abdominal wall defects in rats using collagen scaffolds loaded with collagen-binding basic fibroblast growth factor. Biomaterials 32:753–759PubMedCrossRef
11.
go back to reference Cornwell KG, Pins GD (2010) Enhanced proliferation and migration of fibroblasts on the surface of fibroblast growth factor-2-loaded fibrin microthreads. Tissue Eng Part A 16:3669–3677PubMedCrossRef Cornwell KG, Pins GD (2010) Enhanced proliferation and migration of fibroblasts on the surface of fibroblast growth factor-2-loaded fibrin microthreads. Tissue Eng Part A 16:3669–3677PubMedCrossRef
12.
go back to reference Kalghatgi S, Friedman G, Fridman A, Clyne AM (2010) Endothelial cell proliferation is enhanced by low dose non-thermal plasma through fibroblast growth factor-2 release. Ann Biomed Eng 38:748–757PubMedCrossRef Kalghatgi S, Friedman G, Fridman A, Clyne AM (2010) Endothelial cell proliferation is enhanced by low dose non-thermal plasma through fibroblast growth factor-2 release. Ann Biomed Eng 38:748–757PubMedCrossRef
13.
go back to reference Hirooka T, Fujiwara Y, Inoue S, Shinkai Y, Yamamoto C, Satoh M, Yasutake A, Eto K, Kaji T (2009) Suppression of fibroblast growth factor-2 expression: possible mechanism underlying methylmercury-induced inhibition of the repair of wounded monolayers of cultured human brain microvascular endothelial cells. J Toxicol Sci 34:433–439PubMedCrossRef Hirooka T, Fujiwara Y, Inoue S, Shinkai Y, Yamamoto C, Satoh M, Yasutake A, Eto K, Kaji T (2009) Suppression of fibroblast growth factor-2 expression: possible mechanism underlying methylmercury-induced inhibition of the repair of wounded monolayers of cultured human brain microvascular endothelial cells. J Toxicol Sci 34:433–439PubMedCrossRef
14.
go back to reference Schultz GS, Wysocki A (2009) Interactions between extracellular matrix and growth factors in wound healing. Wound Repair Regen 17:153–162PubMedCrossRef Schultz GS, Wysocki A (2009) Interactions between extracellular matrix and growth factors in wound healing. Wound Repair Regen 17:153–162PubMedCrossRef
15.
go back to reference Nurata H, Cemil B, Kurt G, Uçankuş NL, Dogulu F, Omeroğlu S (2009) The role of fibroblast growth factor-2 in healing the dura mater after inducing cerebrospinal fluid leakage in rats. J Clin Neurosci 16:542–544PubMedCrossRef Nurata H, Cemil B, Kurt G, Uçankuş NL, Dogulu F, Omeroğlu S (2009) The role of fibroblast growth factor-2 in healing the dura mater after inducing cerebrospinal fluid leakage in rats. J Clin Neurosci 16:542–544PubMedCrossRef
16.
go back to reference Xie JL, Bian HN, Qi SH, Chen HD, Li HD, Xu YB, Li TZ, Liu XS, Liang HZ, Xin BR, Huan Y (2008) Basic fibroblast growth factor (bFGF) alleviates the scar of the rabbit ear model in wound healing. Wound Repair Regen 16:576–581PubMedCrossRef Xie JL, Bian HN, Qi SH, Chen HD, Li HD, Xu YB, Li TZ, Liu XS, Liang HZ, Xin BR, Huan Y (2008) Basic fibroblast growth factor (bFGF) alleviates the scar of the rabbit ear model in wound healing. Wound Repair Regen 16:576–581PubMedCrossRef
17.
go back to reference Roberts WE, Chamberlain JG (1978) Scanning electron microscopy of the cellular elements of rat periodontal ligament. Arch Oral Biol 23:587–589PubMedCrossRef Roberts WE, Chamberlain JG (1978) Scanning electron microscopy of the cellular elements of rat periodontal ligament. Arch Oral Biol 23:587–589PubMedCrossRef
18.
go back to reference Kaplan EL, Meier P (1953) Nonparametric estimation from incomplete observations. J Am Stat Assoc 53:457–481CrossRef Kaplan EL, Meier P (1953) Nonparametric estimation from incomplete observations. J Am Stat Assoc 53:457–481CrossRef
19.
go back to reference Furuzono T, Sonoda K, Tanaka J (2001) A hydroxyapatite coating covalently linked onto a silicone implant material. J Biomed Mater Res 56:9–16PubMedCrossRef Furuzono T, Sonoda K, Tanaka J (2001) A hydroxyapatite coating covalently linked onto a silicone implant material. J Biomed Mater Res 56:9–16PubMedCrossRef
20.
go back to reference Furuzono T, Wang PL, Korematsu A, Miyazaki K, Oido-Mori M, Kowashi Y, Ohura K, Tanaka J, Kishida A (2003) Physical and biological evaluations of sintered hydroxyapatite/silicone composite with covalent bonding for a percutaneous implant material. J Biomed Mater Res B Appl Biomater 65:217–226PubMedCrossRef Furuzono T, Wang PL, Korematsu A, Miyazaki K, Oido-Mori M, Kowashi Y, Ohura K, Tanaka J, Kishida A (2003) Physical and biological evaluations of sintered hydroxyapatite/silicone composite with covalent bonding for a percutaneous implant material. J Biomed Mater Res B Appl Biomater 65:217–226PubMedCrossRef
21.
go back to reference Cooper RR, Misol S (1970) Tendon and ligament insertion: a light and electron microscopic study. J Bone Joint Surg Am 52:1–21PubMed Cooper RR, Misol S (1970) Tendon and ligament insertion: a light and electron microscopic study. J Bone Joint Surg Am 52:1–21PubMed
22.
go back to reference Short E, Johnson RB (1990) Effects of tooth function on adjacent alveolar bone and Sharpey’s fibers of the rat periodontium. Anat Rec 227:391–396PubMedCrossRef Short E, Johnson RB (1990) Effects of tooth function on adjacent alveolar bone and Sharpey’s fibers of the rat periodontium. Anat Rec 227:391–396PubMedCrossRef
23.
go back to reference Simmons DJ, Menton DN, Miller S, Lozano R (1993) Periosteal attachment fibers in the rat calvarium. Calcif Tissue Int 53:424–427PubMed Simmons DJ, Menton DN, Miller S, Lozano R (1993) Periosteal attachment fibers in the rat calvarium. Calcif Tissue Int 53:424–427PubMed
24.
go back to reference Murakami S, Takayama S, Ikezawa K, Shimabukuro Y, Kitamura M, Nozaki T, Terashima A, Asano T, Okada H (1999) Regeneration of periodontal tissues by basic fibroblast growth factor. J Periodontal Res 34:425–430PubMedCrossRef Murakami S, Takayama S, Ikezawa K, Shimabukuro Y, Kitamura M, Nozaki T, Terashima A, Asano T, Okada H (1999) Regeneration of periodontal tissues by basic fibroblast growth factor. J Periodontal Res 34:425–430PubMedCrossRef
25.
go back to reference Sato Y, Kikuchi M, Ohata N, Tamura M, Kuboki Y (2004) Enhanced cementum formation in experimentally induced cementum defects of the root surface with the application of recombinant basic fibroblast growth factor in collagen gel in vivo. J Periodontol 75:243–248PubMedCrossRef Sato Y, Kikuchi M, Ohata N, Tamura M, Kuboki Y (2004) Enhanced cementum formation in experimentally induced cementum defects of the root surface with the application of recombinant basic fibroblast growth factor in collagen gel in vivo. J Periodontol 75:243–248PubMedCrossRef
26.
go back to reference Chen YL, Chen PK, Jeng LB, Huang CS, Yang LC, Chung HY, Chang SC (2008) Periodontal regeneration using ex vivo autologous stem cells engineered to express the BMP-2 gene: an alternative to alveoloplasty. Gene Ther 15:1469–1477PubMedCrossRef Chen YL, Chen PK, Jeng LB, Huang CS, Yang LC, Chung HY, Chang SC (2008) Periodontal regeneration using ex vivo autologous stem cells engineered to express the BMP-2 gene: an alternative to alveoloplasty. Gene Ther 15:1469–1477PubMedCrossRef
27.
go back to reference Camelo M, Nevins ML, Lynch SE, Schenk RK, Simion M, Nevins M (2001) Periodontal regeneration with an autogenous bone-Bio-Oss composite graft and a Bio-Gide membrane. Int J Periodontics Restor Dent 21:109–119 Camelo M, Nevins ML, Lynch SE, Schenk RK, Simion M, Nevins M (2001) Periodontal regeneration with an autogenous bone-Bio-Oss composite graft and a Bio-Gide membrane. Int J Periodontics Restor Dent 21:109–119
28.
go back to reference Shirakata Y, Taniyama K, Yoshimoto T, Miyamoto M, Takeuchi N, Matsuyama T, Noguchi K (2010) Regenerative effect of basic fibroblast growth factor on periodontal healing in two-wall intrabony defects in dogs. J Clin Periodontol 37:374–381PubMedCrossRef Shirakata Y, Taniyama K, Yoshimoto T, Miyamoto M, Takeuchi N, Matsuyama T, Noguchi K (2010) Regenerative effect of basic fibroblast growth factor on periodontal healing in two-wall intrabony defects in dogs. J Clin Periodontol 37:374–381PubMedCrossRef
29.
go back to reference Soda Y, Sumen Y, Murakami Y, Ikuta Y, Ochi M (2003) Attachment of autogenous tendon graft to cortical bone is better than to cancellous bone: a mechanical and histological study of MCL reconstruction in rabbits. Acta Orthop Scand 74:322–326PubMedCrossRef Soda Y, Sumen Y, Murakami Y, Ikuta Y, Ochi M (2003) Attachment of autogenous tendon graft to cortical bone is better than to cancellous bone: a mechanical and histological study of MCL reconstruction in rabbits. Acta Orthop Scand 74:322–326PubMedCrossRef
Metadata
Title
Enhanced wound healing associated with Sharpey’s fiber-like tissue formation around FGF-2-apatite composite layers on percutaneous titanium screws in rabbits
Authors
Hirotaka Mutsuzaki
Atsuo Ito
Yu Sogo
Masataka Sakane
Ayako Oyane
Naoyuki Ochiai
Publication date
01-01-2012
Publisher
Springer-Verlag
Published in
Archives of Orthopaedic and Trauma Surgery / Issue 1/2012
Print ISSN: 0936-8051
Electronic ISSN: 1434-3916
DOI
https://doi.org/10.1007/s00402-011-1381-7

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