The calcium phosphate matrix of FGF-2-apatite composite layers contributes to their biological effects.

Hirotaka Mutsuzaki,Ayako Oyane,Yu Sogo,Masashi Yamazaki,Masataka Sakane,Atsuo Ito

doi:10.3390/ijms150610252

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.

Highlights

Pin tract infections and loose anchorages are severe problems that can occur during external fixation [1,2,3,4,5,6,7]
The fibroblast growth factor (FGF)-2-apatite composite layers on the Ti pins coated at 25 °C for 1 day contained similar FGF-2, Ca, and P contents to those coated at 37 °C for 2 days, but the Ca/P molar ratios were significantly different
Further optimization of the fabrication parameters is needed to reduce the bacterial infection rate and improve the fixation strength at the bone-pin interface for the FGF-2-apatite composite layers prepared at 25 °C

Summary

Introduction

Pin tract infections and loose anchorages are severe problems that can occur during external fixation [1,2,3,4,5,6,7]. Preventing pin tract infections is essential for the successful external fixation of bone. Pin tract infections are prevented by intensive pin site care [8]. Modifications of pin surfaces to prevent pin tract infections have been developed, including hydroxyapatite coatings for increasing fixation strength in the bone-pin interface [9,10], as well as a titanium-copper alloy [11], silver coatings [12,13], a titanium oxide photocatalyst coating [14], and antimicrobial-loaded hydroxyapatite [15] and polymer coatings [16]. We formed fibroblast growth factor (FGF)-2-apatite composite layers on titanium (Ti) pins by immersing them in an infusion fluid-based supersaturated calcium phosphate (CaP)

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Conclusion