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Effects of VEGF temporal and spatial presentation on angiogenesis
Eduardo A Silva1, David J Mooney
1Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, MA, USA.
Biomaterials
|November 13, 2009
Summary
Optimizing vascular endothelial growth factor (VEGF) delivery is key for therapeutic angiogenesis. A high initial VEGF concentration followed by a decrease, with dual-site delivery, maximizes vascularization in ischemic tissues.
Area of Science:
- Biomaterials Science
- Regenerative Medicine
- Vascular Biology
Background:
- Therapeutic angiogenesis aims to restore blood flow to ischemic tissues using angiogenic factors.
- Polymeric materials offer controlled delivery of vascular endothelial growth factor (VEGF), but optimal presentation remains unclear.
Purpose of the Study:
- To investigate the impact of VEGF dose, temporal release profile, and spatial distribution on angiogenesis.
- To determine optimal VEGF delivery strategies for treating tissue ischemia.
Main Methods:
- In vitro angiogenesis models were used to analyze VEGF concentration profiles and spatial distribution.
- An in vivo murine hindlimb ischemia model was employed to evaluate therapeutic efficacy.
Main Results:
- An optimal temporal profile involved a high initial VEGF concentration followed by a gradual decrease.
- A total dose of 0.1 microg/g VEGF, delivered with the optimal kinetics, was effective in vivo.
- Dual-site spatial delivery of VEGF resulted in superior vascularization and perfusion compared to single-site delivery.
Conclusions:
- Material systems enabling controlled temporal and spatial VEGF presentation are crucial for potent therapeutic angiogenesis.
- Optimized VEGF delivery strategies can significantly enhance vascular regeneration in ischemic conditions.
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