Vascularization in vivo caused by the controlled release of fibroblast growth factor-2 from an injectable chitosan/non-anticoagulant heparin hydrogel

Biomaterials. 2004 Feb;25(4):699-706. doi: 10.1016/s0142-9612(03)00557-x.

Abstract

Addition of various heparinoids to the lactose-introduced, water-soluble chitosan (CH-LA) aqueous solution produces an injectable chitosan/heparinoid hydrogel. In the present work, we examined the capability of the chitosan/non-anticoagulant heparin (periodate-oxidized (IO(4)-) heparin) hydrogel to immobilize fibroblast growth factor (FGF)-2, as well as the controlled release of FGF-2 molecules from the hydrogel in vitro and in vivo. The hydrogel was biodegraded in about 20 days after subcutaneous injection into the back of a mouse. When the FGF-2-incorporated hydrogel was subcutaneously injected into the back of both mice and rats, a significant neovascularization and fibrous tissue formation were induced near the injected site. These results indicate that the controlled release of biologically active FGF-2 molecules is caused by biodegradation of the hydrogel, and that subsequent induction of the vascularization occurs.

Publication types

  • Evaluation Study

MeSH terms

  • Animals
  • Chitin / analogs & derivatives*
  • Chitin / chemistry*
  • Chitosan
  • Coated Materials, Biocompatible / administration & dosage*
  • Coated Materials, Biocompatible / chemistry*
  • Delayed-Action Preparations / administration & dosage*
  • Endothelial Cells / cytology
  • Endothelial Cells / drug effects
  • Female
  • Fibroblast Growth Factor 2 / administration & dosage*
  • Fibroblast Growth Factor 2 / chemistry
  • Heparinoids / chemistry*
  • Humans
  • Hydrogels / chemistry*
  • Injections
  • Male
  • Materials Testing
  • Mice
  • Neovascularization, Physiologic / drug effects*
  • Neovascularization, Physiologic / physiology
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Coated Materials, Biocompatible
  • Delayed-Action Preparations
  • Heparinoids
  • Hydrogels
  • Fibroblast Growth Factor 2
  • Chitin
  • Chitosan