Effects of VEGF temporal and spatial presentation on angiogenesis

Eduardo Silva, David J. Mooney

Research output: Contribution to journalArticle

146 Scopus citations

Abstract

Therapeutic angiogenesis relies on the delivery of angiogenic factors capable of reversing tissue ischemia. Polymeric materials that can provide spatial and temporal over vascular endothelial growth factor (VEGF) presentation provide clear benefit, but the influence of VEGF dose, temporal, and spatial presentation on the resultant angiogenic process are largely unknown. The influence of the temporal profile of VEGF concentration, dose, and the impact of VEGF spatial distribution on angiogenesis in in vitro models of angiogenesis and ischemic murine limbs was analyzed in this study. Importantly, a profile consisting of a high VEGF concentration initially, followed by a decreasing concentration over time was found to yield optimal angiogenic sprouting. A total VEGF dose 0.1 μg/g, when delivered with kinetics found to be optimal in vitro, provided a favorable therapeutic dose in murine hindlimb ischemia model, and distributing this VEGF dose in two spatial locations induces a higher level of vascularization and perfusion than a single location. These findings suggest that material systems capable of controlling and regulating the temporal and spatial presentation of VEGF maybe useful to achieve a robust and potent therapeutic angiogenic effect in vivo.

Original languageEnglish (US)
Pages (from-to)1235-1241
Number of pages7
JournalBiomaterials
Volume31
Issue number6
DOIs
StatePublished - Feb 1 2010
Externally publishedYes

Keywords

  • Peripheral vascular diseases (PVD)
  • Poly(lactide-co-glycolide)
  • Polymer
  • Regenerative medicine
  • Sustained delivery
  • Synthetic extracellular matrices

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics

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