Journal
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
Volume 298, Issue 6, Pages H1959-H1965Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.00199.2009
Keywords
tissue engineering; angiogenesis; arteriogenesis; vascular endothelial growth factor; poly(lactic-co-glycolic acid)
Funding
- Georgia Tech/Emory Center for the Engineering of Living Tissues
- National Science Foundation [EEC-9731643]
- National Institutes of Health [AR-051336, U01-HL-080711, R01-HL-70531]
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Golub JS, Kim Y, Duvall CL, Bellamkonda RV, Gupta D, Lin AS, Weiss D, Taylor WR, Guldberg RE. Sustained VEGF delivery via PLGA nanoparticles promotes vascular growth. Am J Physiol Heart Circ Physiol 298: H1959-H1965, 2010. First published March 12, 2010; doi:10.1152/ajpheart.00199.2009.-Technologies to increase tissue vascularity are critically important to the fields of tissue engineering and cardiovascular medicine. Currently, limited technologies exist to encourage angiogenesis and arteriogenesis in a controlled manner. In the present study, we describe an injectable controlled release system consisting of VEGF encapsulated in poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs). The majority of VEGF was released gradually over 2-4 days from the NPs as determined by an ELISA release kinetics experiment. An in vitro aortic ring bioassay was used to verify the bioactivity of VEGF-NPs compared with empty NPs and no treatment. A mouse femoral artery ischemia model was then used to measure revascularization in VEGF-NP-treated limbs compared with limbs treated with naked VEGF and saline. 129/Sv mice were anesthetized with isoflurane, and a region of the common femoral artery and vein was ligated and excised. Mice were then injected with VEGF-NPs, naked VEGF, or saline. After 4 days, three-dimensional microcomputed tomography angiography was used to quantify vessel growth and morphology. Mice that received VEGF-NP treatment showed a significant increase in total vessel volume and vessel connectivity compared with 5 mu g VEGF, 2.5 mu g VEGF, and saline treatment (all P < 0.001). When the yield of the fabrication process was taken into account, VEGF-NPs were over an order of magnitude more potent than naked VEGF in increasing blood vessel volume. Differences between the VEGF-NP group and all other groups were even greater when only small-sized vessels under 300 mu m diameter were analyzed. In conclusion, sustained VEGF delivery via PLGA NPs shows promise for encouraging blood vessel growth in tissue engineering and cardiovascular medicine applications.
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