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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Abbreviations
- Empty-PLG:
-
PLG polymer not loaded with growth factor
- ∅-Implant:
-
hind limb surgery performed with no PLG polymer implanted
- PAD:
-
peripheral arterial disease
- PLG:
-
poly(lactide-co-glycolide)
- PLG-VEGF:
-
PLG polymer loaded with 3 μg of VEGF165
- SMA:
-
smooth muscle actin
- VEGF:
-
vascular endothelial growth factor
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Acknowledgement
This work was financially supported by the National Heart, Lung and Blood Institute (R01 HL069957).
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Sun, Q., Chen, R.R., Shen, Y. et al. Sustained Vascular Endothelial Growth Factor Delivery Enhances Angiogenesis and Perfusion in Ischemic Hind Limb. Pharm Res 22, 1110–1116 (2005). https://doi.org/10.1007/s11095-005-5644-2
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DOI: https://doi.org/10.1007/s11095-005-5644-2