A bilayer small diameter in vitro vascular model for evaluation of drug induced vascular injury

David M. Hoganson, Eric B. Finkelstein, Gwen E. Owens, James C. Hsiao, Kurt Y. Eng, Katherine M. Kulig, Ernest S. Kim, Tatiana Kniazeva, Irina Pomerantseva, Craig M. Neville, James R. Turk, Bernard Fermini, Jeffrey T. Borenstein, Joseph P. Vacanti

Research output: Contribution to journalArticle

Abstract

In pre-clinical safety studies, drug-induced vascular injury (DIVI) is defined as an adverse response to a drug characterized by degenerative and hyperplastic changes of endothelial cells and vascular smooth muscle cells. Inflammation may also be seen, along with extravasation of red blood cells into the smooth muscle layer (i.e., hemorrhage). Drugs that cause DIVI are often discontinued from development after considerable cost has occurred. An in vitro vascular model has been developed using endothelial and smooth muscle cells in co-culture across a porous membrane mimicking the internal elastic lamina. Arterial flow rates of perfusion media within the endothelial chamber of the model induce physiologic endothelial cell alignment. Pilot testing with a drug known to cause DIVI induced extravasation of red blood cells into the smooth muscle layer in all devices with no extravasation seen in control devices. This engineered vascular model offers the potential to evaluate candidate drugs for DIVI early in the discovery process. The physiologic flow within the coculture model also makes it candidate for a wide variety of vascular biology investigations.

Original languageEnglish (US)
Article number054116
JournalBiomicrofluidics
Volume10
Issue number5
DOIs
StatePublished - Sep 1 2016

ASJC Scopus subject areas

  • Biomedical Engineering
  • Materials Science(all)
  • Condensed Matter Physics
  • Fluid Flow and Transfer Processes
  • Colloid and Surface Chemistry

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  • Cite this

    Hoganson, D. M., Finkelstein, E. B., Owens, G. E., Hsiao, J. C., Eng, K. Y., Kulig, K. M., Kim, E. S., Kniazeva, T., Pomerantseva, I., Neville, C. M., Turk, J. R., Fermini, B., Borenstein, J. T., & Vacanti, J. P. (2016). A bilayer small diameter in vitro vascular model for evaluation of drug induced vascular injury. Biomicrofluidics, 10(5), [054116]. https://doi.org/10.1063/1.4964814