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

Int J Mol Sci. 2014 Jun 10;15(6):10252-70. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apatites / chemistry*
  • Bone Nails / adverse effects
  • Bone Nails / microbiology
  • Bone and Bones / pathology
  • Calcium Phosphates / chemistry*
  • Coated Materials, Biocompatible / chemistry*
  • Coated Materials, Biocompatible / metabolism
  • Escherichia coli / isolation & purification
  • Fibroblast Growth Factor 2 / chemistry*
  • Fibroblast Growth Factor 2 / metabolism
  • Inflammation / etiology
  • Male
  • Mice
  • NIH 3T3 Cells
  • Osteomyelitis / metabolism
  • Osteomyelitis / microbiology
  • Osteomyelitis / pathology
  • Rabbits
  • Staphylococcus aureus / isolation & purification
  • Titanium / chemistry

Substances

  • Apatites
  • Calcium Phosphates
  • Coated Materials, Biocompatible
  • Fibroblast Growth Factor 2
  • calcium phosphate
  • Titanium