International Journal of Molecular Sciences, Vol.15, No.6, 10252-10270, 2014
The Calcium Phosphate Matrix of FGF-2-Apatite Composite Layers Contributes to Their Biological Effects
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 degrees 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 degrees C. Ti pins were immersed in a supersaturated CaP solution containing 0.5, 1.0, or 2.0 mu g/mL FGF-2 at 25 degrees C for 24 h (25F0.5, 25F1.0, and 25F2.0) or containing 4.0 mu g/mL FGF-2 at 37 degrees 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 degrees C (1.55-1.56 +/- 0.01-0.02, p = 0.0008-0.0045) than at 37 degrees 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 degrees 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 degrees 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.
Keywords:fibroblast growth factor 2;apatite coating;pin tract infection;external fixation;fixation strength;Ca/P molar ratio