Sustained Vascular Endothelial Growth Factor Delivery Enhances Angiogenesis and Perfusion in Ischemic Hind Limb
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- Sun, Q., Chen, R.R., Shen, Y. et al. Pharm Res (2005) 22: 1110. doi:10.1007/s11095-005-5644-2
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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.
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.
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).
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.
Key Wordsangiogenesis ischemia polymer vascular endothelial growth factor
PLG polymer not loaded with growth factor
hind limb surgery performed with no PLG polymer implanted
peripheral arterial disease
PLG polymer loaded with 3 μg of VEGF165
smooth muscle actin
vascular endothelial growth factor