Heparin-modified dendrimer cross-linked collagen matrices for the delivery of basic fibroblast growth factor (FGF-2)

J Biomater Sci Polym Ed. 2008;19(9):1201-18. doi: 10.1163/156856208785540181.

Abstract

Tissue integration between a tissue-engineered corneal equivalent and the host eye is of critical importance in ensuring long-term implant success. A novel dendrimer cross-linked collagen scaffold has previously shown good corneal epithelial cell compatibility in vitro particularly when the highly functional dendrimer cross-linkers were functionalized to introduce additional biological groups. Herein we investigated heparinization of these materials and their potential to facilitate the delivery of basic fibroblast growth factor (FGF-2) in an active form, ultimately for use as a corneal tissue scaffold. Collagen gels cross-linked with 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) chemistry, and varying amounts of polypropyleneimine octaamine generation 2 (G2) dendimer and heparin were synthesized. Swelling studies and differential scanning calorimetry characterization indicated higher gel stability with the introduction of dendrimer cross-linking, which was not compromised by heparin integration. Dendrimer cross-linked gels with or without heparin gave multiple denaturation peaks, as did the heparinized EDC gels. This is thought to be the result of the heterogeneous cross-linking possible between collagen, the dendrimer and heparin. Release of FGF-2 from collagen gels showed typical first-order kinetics, with an initial burst followed by a prolonged gradual release. Heparinized dendrimer cross-linked gels released approx. 40% of the growth factor over a 2-week period, with significance maintenance of growth factor activity. Incorporation of heparin resulted in somewhat prolonged release from these systems.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biocompatible Materials / chemistry
  • Biocompatible Materials / metabolism
  • Collagen / chemistry*
  • Collagen / metabolism
  • Cornea / cytology
  • Cross-Linking Reagents / chemistry
  • Dendrimers / chemistry*
  • Drug Carriers* / chemistry
  • Drug Carriers* / metabolism
  • Fibroblast Growth Factor 2 / genetics
  • Fibroblast Growth Factor 2 / metabolism*
  • Gels / chemistry*
  • Gels / metabolism
  • Heparin / chemistry
  • Heparin / metabolism*
  • Materials Testing
  • Molecular Structure
  • Protein Denaturation
  • Stromal Cells / cytology
  • Tissue Engineering

Substances

  • Biocompatible Materials
  • Cross-Linking Reagents
  • Dendrimers
  • Drug Carriers
  • Gels
  • Fibroblast Growth Factor 2
  • Heparin
  • Collagen