title: A bilayer small diameterin vitrovascular model for evaluation of drug induced vascular injury.
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. Anin vitrovascular 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 co-culture model also makes it candidate for a wide variety of vascular biology investigations.
authors: David M
authors: 0000-0002-8141-7793
authors: DM
authors: Hoganson
authors: Syracuse Biomaterials Institute and Department of Biomedical and Chemical Engineering, Syracuse University , Syracuse, New York 13244, USA.
authors: Eric B
authors: EB
authors: Finkelstein
authors: Center for Regenerative Medicine, Department of Surgery, Massachusetts General Hospital , Boston, Massachusetts 02114, USA.
authors: Gwen E
authors: GE
authors: Owens
authors: Draper Laboratories , Cambridge, Massachusetts 02139, USA.
authors: James C
authors: JC
authors: Hsiao
authors: Pfizer Inc. , Cambridge, Massachusetts 02139, USA.
authors: Kurt Y
authors: 0000-0002-6445-4891
authors: KY
authors: Eng
authors: Center for Regenerative Medicine, Department of Surgery, Massachusetts General Hospital , Boston, Massachusetts 02114, USA.
authors: Katherine M
authors: KM
authors: Kulig
authors: Draper Laboratories , Cambridge, Massachusetts 02139, USA.
authors: Ernest S
authors: ES
authors: Kim
authors: Draper Laboratories , Cambridge, Massachusetts 02139, USA.
authors: Tatiana
authors: T
authors: Kniazeva
authors: Center for Regenerative Medicine, Department of Surgery, Massachusetts General Hospital , Boston, Massachusetts 02114, USA.
authors: Irina
authors: I
authors: Pomerantseva
authors: Center for Regenerative Medicine, Department of Surgery, Massachusetts General Hospital , Boston, Massachusetts 02114, USA.
authors: Craig M
authors: CM
authors: Neville
authors: Amgen , Thousand Oaks, California 91320, USA.
authors: James R
authors: JR
authors: Turk
authors: Pfizer Inc. , Groton, Connecticut 06340, USA.
authors: Bernard
authors: B
authors: Fermini
authors: Draper Laboratories , Cambridge, Massachusetts 02139, USA.
authors: Jeffrey T
authors: JT
authors: Borenstein
authors: Center for Regenerative Medicine, Department of Surgery, Massachusetts General Hospital , Boston, Massachusetts 02114, USA.
authors: Joseph P
authors: JP
authors: Vacanti