Development of a prostacyclin-agonist–eluting aortic stent graft enhancing biological attachment to the aortic wall

Abstract

Stent graft-related complications, including endoleaks and graft migration, are partly attributed to insufficient graft attachment to the aortic wall. ONO-1301, a stable synthetic prostacyclin agonist, reportedly reorganizes extracellular matrices, enhancing tissue healing. We hypothesized that ONO-1301-eluting stent grafts may strengthen graft attachment to the aortic wall. Polylactic acid polymer-conjugated ONO-1301, which releases ONO-1301 into adjacent tissues over 3 months (ONO(+) group), or polylactic acid polymer only (ONO(-) group) was coated onto the stent graft and placed in the descending thoracic aorta of canines weighing 16 to 20 kg under fluoroscopic guidance. Examinations occurred at 1, 2, or 3 months postoperatively (n = 6 for each time point and group). ONO-1301 aortic-wall concentrations were within the effective range even at 3 months. The maximal load for tearing the graft from the aortic wall ex vivo was significantly greater in the ONO(+) group than in the ONO(-) group (117.1%±44.4%, 133.9%±23.2%, and 119.9%±13.5% at 1, 2, and 3 months, respectively; P=.0007). Immunohistochemical examination revealed abundant α-smooth muscle actin-positive cells in the neointima in both groups. The fibrotic area between the graft and the aortic wall was significantly larger (P<.0001), and migrating cells into the graft fabric were significantly greater (P=.0003) in the ONO(+) group than in the ONO(-) group. In canines, the ONO-1301-eluting stent graft enhanced tissue reorganization and improved the attachment between the graft and the aortic wall. This new device may be useful in preventing inadequate graft attachment to the aortic wall.