Sustained Vascular Endothelial Growth Factor Delivery Enhances Angiogenesis and Perfusion in Ischemic Hind Limb |
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Authors: | Qinghua?Sun,Ruth?R.?Chen,Yuechun?Shen,David?J.?Mooney,Sanjay?Rajagopalan,P.?Michael?Grossman author-information" > author-information__contact u-icon-before" > mailto:pagross@umich.edu" title=" pagross@umich.edu" itemprop=" email" data-track=" click" data-track-action=" Email author" data-track-label=" " >Email author |
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Affiliation: | (1) Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan Hospitals and Health System, Ann Arbor, Michigan 48109-0311, USA;(2) Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, Michigan 48109, USA |
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Abstract: | Purpose We hypothesized that sustained delivery of vascular endothelial growth factor (VEGF) using a polymer [85:15 poly(lactide-co-glycolide) (PLG)] would enhance angiogenesis and improve perfusion of ischemic tissue.Methods C57BL/6J mice (n = 20/group) underwent unilateral hind limb ischemia surgery and were randomized to groups of no scaffold implantation (∅-Implant), unloaded scaffold implantation (Empty-PLG), or implantation of scaffolds incorporating 3 μg of VEGF165 (PLG-VEGF). Endpoints included laser Doppler perfusion imaging (LDPI, ischemic/nonischemic limb, %), local vessel counts, immunohistochemistry for CD31, and α-smooth muscle actin. In vitro release kinetics of VEGF from PLG was also measured.Results PLG-VEGF resulted in improved lower extremity perfusion vs. controls as measured by LDPI% at 7, 14, 21, and 28 days (p < 0.05). PLG-VEGF was associated with significantly greater percentage of vessels staining for CD31 and α-smooth muscle actin compared to the Empty-PLG or ∅-Implant (p < 0.05 for both).Conclusions The PLG-VEGF scaffolds resulted in sustained VEGF delivery, improved tissue perfusion, greater capillary density, and more mature vasculature compared to the controls. The sustained-release PLG polymer vehicle is a promising delivery system for therapeutic neovascularization applications. |
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Keywords: | angiogenesis ischemia polymer vascular endothelial growth factor |
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