title: The calcium phosphate matrix of FGF-2-apatite composite layers contributes to their biological effects.
abstract: The purpose of the present study was to fabricate fibroblast growth factor (FGF)-2-apatite composite layers on titanium (Ti) pins in one step at 25 °C using a supersaturated calcium phosphate (CaP) solution, and to evaluate the physicochemical characteristics and biological effects of the coated Ti pins compared with coated Ti pins fabricated at 37 °C. Ti pins were immersed in a supersaturated CaP solution containing 0.5, 1.0, or 2.0 µg/mL FGF-2 at 25 °C for 24 h (25F0.5, 25F1.0, and 25F2.0) or containing 4.0 µg/mL FGF-2 at 37 °C for 48 h (37F4.0). Except for the 25F0.5, the chemical compositions and the mitogenic activity levels of FGF-2 of the composite layers formed by these two methods were similar, except for the Ca/P molar ratio, which was markedly smaller at 25 °C (1.55-1.56±0.01-0.02, p=0.0008-0.0045) than at 37 °C (1.67±0.11). Thus, either the apatite was less mature or the amount of amorphous calcium phosphate was higher in the composite layer formed at 25 °C. In vivo, the pin tract infection rate by visual inspection for 37F4.0 (45%) was lower than that for 25F1.0 (80%, p=0.0213), and the rate of osteomyelitis for 37F4.0 (35%) was lower than that for 25F0.5 (75%, p=0.0341). The extraction torque for 37F4.0 (0.276±0.117 Nm) was higher than that for 25F0.5 (0.192±0.117 Nm, p=0.0142) and that for 25F1.0 (0.176±0.133 Nm, p=0.0079). The invasion rate of S. aureus for 37F4.0 (35%) was lower than that for 25F0.5 (75%, p=0.0110). On the whole, the FGF-2-apatite composite layer formed at 25 °C tended to be less effective at improving fixation strength in the bone-pin interface and resisting pin tract infections. These results suggest that the chemistry of the calcium phosphate matrix that embeds FGF-2, in addition to FGF-2 content and activity, has a significant impact on composite infection resistance and fixation strength.
authors.affiliation: Department of Orthopaedic Surgery, Ibaraki Prefectural University of Health Sciences, 4669-2 Ami Ami-machi, Inashiki-gun, Ibaraki 300-0394, Japan. yu-sogou@aist.go.jp.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Mutsuzaki
authors.affiliation: Human Technology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Central 6, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan. atsuo-ito@aist.go.jp.
authors.forename: Atsuo
authors.initials: A
authors.lastname: Ito
authors.affiliation: Human Technology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Central 6, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan. yu-sogou@aist.go.jp.
authors.forename: Yu
authors.initials: Y
authors.lastname: Sogo
authors.affiliation: Department of Orthopaedic Surgery, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan. sakane-m@md.tsukuba.ac.jp.
authors.forename: Masataka
authors.initials: M
authors.lastname: Sakane
authors.affiliation: Nanosystem Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Central 4, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8562, Japan. a-oyane@aist.go.jp.
authors.forename: Ayako
authors.initials: A
authors.lastname: Oyane
authors.affiliation: Department of Orthopaedic Surgery, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan. masashiy@md.tsukuba.ac.jp.
authors.forename: Masashi
authors.initials: M
authors.lastname: Yamazaki
mesh_terms: D000818:Animals; D001031:Apatites / Q000737:chemistry*; D001858:Bone Nails / Q000009:adverse effects / Q000382:microbiology; D001842:Bone and Bones / Q000473:pathology; D002130:Calcium Phosphates / Q000737:chemistry*; D020099:Coated Materials, Biocompatible / Q000737:chemistry* / Q000378:metabolism; D004926:Escherichia coli / Q000302:isolation & purification; D016222:Fibroblast Growth Factor 2 / Q000737:chemistry* / Q000378:metabolism; D007249:Inflammation / Q000209:etiology; D008297:Male; D051379:Mice; D041681:NIH 3T3 Cells; D010019:Osteomyelitis / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D011817:Rabbits; D013211:Staphylococcus aureus / Q000302:isolation & purification; D014025:Titanium / Q000737:chemistry
chemical_list: D001031:Apatites; D002130:Calcium Phosphates; D020099:Coated Materials, Biocompatible; D016222:Fibroblast Growth Factor 2; C020243:calcium phosphate; D014025:Titanium