PROJECT SUMMARY
Over 250,000 angioplasties, stents and open bypasses are performed each year to open occluded vessels for
preservation of life and limb, yet over half of these will fail in under 5 years due to restenosis. The underlying
pathology of restenosis is cellular proliferation that re-narrows the vessel lumen. Restenosis increases the
cost and complications of re-intervention, as well as risking cardiac ischemia, stroke and limb loss. Current
treatment involves a balloon coated with an anti-proliferative drug that is delivered to the vessel wall by direct
contact. Drug coated balloons (DCB) present several limitations including: 1) Technical limits to the type and
amount of drug that can be adhered to a balloon 2) Much of the drug is lost simply by inserted the DCB into
the bloodstream. 3) The occlusive nature of DCB limits the time it can transfer the drug without distal
ischemia. The overarching problem is the inability to deliver high intensity intravascular therapeutics,
while minimizing losses to the circulation that might otherwise be costly or toxic at the systemic level.
A Retrievable Drug Delivery Stentgraft (RDDS) is a novel, dumbbell shaped stent covered in polymer. A
center lumen preserves distal perfusion, while an isolated outer chamber isolates the vascular target. The
RDDS would infuse drug only after the target has been isolated by the stent outer chamber, with aspiration of
unused drug prior to stent removal, thereby reducing systemic losses and toxicity. The design of the RDDS
could accomodate larger quantities of drug and also liquid agents. By preserving distal perfusion, the RDDS
can offer longer incubation of the drug with the vessel wall, contrasting to occlusive DCB that otherwise risk
distal ischemia. The RDDS bears some important distinctions to current permanent drug eluting stents, which
are at risk of circulatory drug loss, should not be used at vascular branches or areas of anatomic flexion, incur
thrombosis over poorly re-endothelialized stent struts and carry traditional risks of a permanent implant. By
contrast, the RDDS is removed after used by sheath advancement to collapse the stent. As a result, the
RDDS is more comparable to DCB since it delivers a therapeutic without leaving an implant.
This study will first compare the RDDS to DCB in a bioreactor, as well as a porcine model of neointimal
hyperplasia, using assays such as quantitative mass spectrometry of both drug delivery and drug losses,
histologic assessment of arterial healing and restenosis. We hypothesize that the RDDS will reduce circulatory
losses of the anti-restenotic agent paclitaxel (PXL), increase the amount of PXL delivered to the vessel wall,
allow doses of PXL that are not possible with DCB, increase the duration of PXL exposure to the vessel wall,
and reduce intimal hyperplasia more effectively than DCB. More broadly, the beneficial effect of many other
intravascular therapeutics is limited by their systemic toxicity. A vehicle to focus drugs to a specified region
(vascular wall or vascular bed) could improve outcomes while reducing complications in a variety of medical
conditions (e.g. chemotherapy, vasoactive agents, gene vectors, and immunomodulatory agents).
