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Novel Angiogenic Compounds for Targeted Drug Delivery

Published online by Cambridge University Press:  01 February 2011

Kristen A. Wieghaus
Affiliation:
Department of Biomedical Engineering, University of Virginia, Box 800759, Health System, 415. Lane Road, MR-5 Building, Charlottesville, VA 22908
Scott M. Capitosti
Affiliation:
Department of Chemistry, University of Virginia, Box 800759, Health System, 415. Lane Road, MR-5 Building, Charlottesville, VA 22908
Milton L. Brown
Affiliation:
Department of Chemistry, University of Virginia, Box 800759, Health System, 415. Lane Road, MR-5 Building, Charlottesville, VA 22908
Edward A. Botchwey
Affiliation:
Department of Biomedical Engineering, University of Virginia, Box 800759, Health System, 415. Lane Road, MR-5 Building, Charlottesville, VA 22908
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Abstract

Induction of angiogenesis is necessary for the success of engineered implantable tissues in order to meet oxygen and nutrient requirements of cells during tissue repair. Insufficient vascularization in bone graft reconstruction may impede healing and initiate hypoxic cell death at the interior of the implant. As a result, endogenous growth factors have been studied to enhance angiogenesis during wound repair. However, these peptide-based molecules are highly sensitive to processing that occurs during scaffold biomaterial fabrication and treatment for tissue engineering purposes. We report here the development of new small molecule regulators of angiogenesis that may circumvent the impediments associated with protein-based growth factor delivery. In this study, we report the design and evaluation of SC–3–143 as a regulator of endothelial function. We show that the compound significantly increases the formation of microvascular networks in vitro, and selectively enhances endothelial survivability by reducing endothelial cell death under serum deprived culture conditions.

Type
Research Article
Copyright
Copyright © Materials Research Society 2005

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References

REFERENCES

1 Carmliet, P. (2000) Nat. Med. 6, 11021103.Google Scholar
2 Ferrara, N., & Alitalo, K. (1999) Nat. Med. 5, 13591364.Google Scholar
3 Yancopoulos, G.D., Davis, S., Gale, N.W., Rudge, J.S., Wiegand, S.J., & Holash, J. (2000) Nature 407, 242248.Google Scholar
4 D'Amato, R.J., Loughnan, M.S., Flynn, E., & Folkman, J. (1994) Proc. Natl. Acad. Sci. USA 91, 9, 40824085.Google Scholar
5 Rajkumar, S.V., Dispenzieri, A., Fonseca, R., Lacy, M.Q., Geyer, S., Lust, J.A., Kyle, R.A., Griepp, P.R., Gertz, M.A., & Witzig, T.E. (2001) Leukemia 15, 8, 12741276.Google Scholar
6 Wieghaus, K.A., Capitosti, S.M., Blackman, B.R., Brown, M.L., and Botchwey, E.A. Submitted work.Google Scholar
7 Chen, J., Wan, X., Zhu, J., Shang, Y., Guo, X., & Sun, J. (2004) J. Cardiovasc. Pharmacol. 43, 3, 347352.Google Scholar
8 Sung, H.-J., Meredith, C., Johnson, C., & Galis, Z.S. (2004) Biomaterials 25, 57355742.Google Scholar
9 Cleland, J.L., Powell, M.F., & Shire, S.J. (1993) Crit. Rev. Ther. Drug. Carrier Sys. 10, 307377.Google Scholar
10 Peters, M.C., Polverini, P.J., & Mooney, D.J. (2002) J. Biomed. Mat. Res. 60, 668678.Google Scholar