Acceleration of bone formation during fracture healing by injectable collagen powder and human basic fibroblast growth factor containing a collagen-binding domain from Clostridium histolyticum collagenase

J Biomed Mater Res A. 2014 Sep;102(9):3049-55. doi: 10.1002/jbm.a.34974. Epub 2013 Oct 9.

Abstract

Growth factor delivered with implantable biomaterials has been used to both accelerate and ensure healing of open fractures in human patients. However, a major limitation of implantable biomaterials is the requirement for open surgical placement. Here, we developed an injectable collagen material-based bone formation system consisting of injectable collagen powder with fibril morphology and collagen triple helix conformation, and basic fibroblast growth factor (bFGF) fused to the collagen-binding domain (CBD) of Clostridium histolyticum collagenase. The affinity of the CBD towards collagen was confirmed by the results of collagen-binding assays. Moreover, the combination of the collagen binding-bFGF fusion protein (CB-bFGF) with injectable collagen powder induced bone formation at protein concentrations lower than those required for bFGF alone in mice fracture models. Taken together, these properties suggest that the CB-bFGF/collagen powder composite is a promising injectable material for bone repair in the clinical setting.

Keywords: Basic fibroblast growth factor; collagen-binding domain; collagenase; fracture healing; injectable collagen power.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bony Callus / anatomy & histology
  • Bony Callus / drug effects
  • Clostridium / enzymology*
  • Collagen / administration & dosage
  • Collagen / metabolism
  • Collagen / therapeutic use*
  • Fibroblast Growth Factor 2 / administration & dosage
  • Fibroblast Growth Factor 2 / chemistry
  • Fibroblast Growth Factor 2 / pharmacology
  • Fibroblast Growth Factor 2 / therapeutic use*
  • Fracture Healing / drug effects*
  • Humans
  • Injections
  • Male
  • Mice
  • Microbial Collagenase / chemistry*
  • Microbial Collagenase / metabolism
  • Protein Structure, Tertiary
  • Rats
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / pharmacology
  • Recombinant Proteins / therapeutic use

Substances

  • Recombinant Proteins
  • Fibroblast Growth Factor 2
  • Collagen
  • Microbial Collagenase