The effect of the controlled release of basic fibroblast growth factor from ionic gelatin-based hydrogels on angiogenesis in a murine critical limb ischemic model

Hans Layman, Maria Grazia Spiga, Toby Brooks, Si Pham, Keith A. Webster, Fotios M. Andreopoulos

Research output: Contribution to journalArticle

61 Scopus citations

Abstract

The localized delivery of exogenous, angiogenic growth factors has become a promising alternative treatment of peripheral artery disease (PAD) and critical limb ischemia. In the present study, we describe the development of a novel controlled release vehicle to promote angiogenesis in a murine critical limb ischemic model. Ionic, gelatin-based hydrogels were prepared by the carbodiimide-mediated amidation reaction between the carboxyl groups of gelatin or poly-l-glutamic acid molecules and the amine groups of poly-l-lysine or gelatin molecules, respectively. The degree of swelling of the synthesized hydrogels was assessed as a function of EDC/NHS ratios and the pH of the equilibrating medium, while the release kinetic profile of basic fibroblast growth factor (FGF-2) was evaluated in human fibroblast cultures. The degree of swelling (DS) decreased from 26.5±1.7 to 18.5±2.4 as the EDC concentration varied from 0.75 to 2.5 mg/ml. Eighty percent of the FGF-2 was released at controlled rates from gelatin-polylysine (gelatin-PLL) and gelatin-polyglutamic acid (gelatin-PLG) hydrogel scaffolds over a period of 28 days. Cell adhesion studies revealed that the negatively charged surface of the gelatin-PLG hydrogels exhibited superior adhesion capabilities in comparison to gelatin-PLL and control gelatin surfaces. Laser Doppler perfusion imaging as well as CD31+ capillary immunostaining demonstrated that the controlled release of FGF-2 from ionic gelatin-based hydrogels is superior in promoting angiogenesis in comparison to the bolus administration of the growth factor. Over 4 weeks, FGF-2 releasing gelatin-PLG hydrogels exhibited marked reperfusion with a Doppler ratio of 0.889 (±0.04) which was 69.3% higher than in the control groups.

Original languageEnglish (US)
Pages (from-to)2646-2654
Number of pages9
JournalBiomaterials
Volume28
Issue number16
DOIs
StatePublished - Jun 2007

Keywords

  • Angiogenesis
  • Controlled delivery
  • Critical limb ischemia
  • FGF-2
  • Hydrogels

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering

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