Spatiotemporal control of vascular endothelial growth factor delivery from injectable hydrogels enhances angiogenesis

Eduardo Silva, David J. Mooney

Research output: Contribution to journalArticle

221 Citations (Scopus)

Abstract

Therapeutic angiogenesis with vascular endothelial growth factor (VEGF) delivery may provide a new approach for the treatment of ischemic diseases, but current strategies to deliver VEGF rely on either bolus delivery or systemic administration, resulting in limited clinical utility, because of the short half-life of VEGF in vivo and its resultant low and transient levels at sites of ischemia. We hypothesize that an injectable hydrogel system can be utilized to provide temporal control and appropriate spatial biodistribution of VEGF in ischemic hindlimbs. A sustained local delivery of relatively low amounts of bioactive VEGF (3 μg) with this system led to physiologic levels of bioactive VEGF in ischemic murine (ApoE-/-) hindlimbs for 15 days after injection of the gel, as contrasted with complete VEGF deprivation after 72 h with bolus injection. The gel delivery system resulted in significantly greater angiogenesis in these limbs as compared to bolus (266 vs. 161 blood vessels mm-2). Laser Doppler perfusion imaging showed return of tissue perfusion to normal levels by day 28 with the gel system, whereas normal levels of perfusion were never achieved with saline delivery of VEGF or in control mice. The system described in this article could represent an attractive new generation of therapeutic delivery vehicle for treatment of cardiovascular diseases, as it combines long-term in vivo therapeutic benefit (localized bioactive VEGF for 1-2 weeks) with minimally invasive delivery.

Original languageEnglish (US)
Pages (from-to)590-598
Number of pages9
JournalJournal of Thrombosis and Haemostasis
Volume5
Issue number3
DOIs
StatePublished - Mar 1 2007
Externally publishedYes

Fingerprint

Hydrogels
Vascular Endothelial Growth Factor A
Injections
Gels
Hindlimb
Perfusion
Therapeutics
Perfusion Imaging
Hydrogel
Apolipoproteins E
Blood Vessels
Half-Life
Lasers
Cardiovascular Diseases
Ischemia
Extremities

Keywords

  • Ischemic tissues
  • Peripheral vascular diseases
  • Regenerative medicine
  • Sustained and localized delivery
  • Synthetic extracellular matrices
  • Therapeutic agents

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Spatiotemporal control of vascular endothelial growth factor delivery from injectable hydrogels enhances angiogenesis. / Silva, Eduardo; Mooney, David J.

In: Journal of Thrombosis and Haemostasis, Vol. 5, No. 3, 01.03.2007, p. 590-598.

Research output: Contribution to journalArticle

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