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

OBJECTIVES: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Tissue-engineered stent-graft integrates with aortic wall by recruiting host tissue into graft scaffold.

OBJECTIVE: To prevent postoperative migration and endoleaks after endovascular aneurysm repair, we developed a tissue-engineered vascular graft that integrates with the aortic wall by recruiting the host tissue into the graft scaffold. In the present study, we assessed the mechanical properties of the new graft and evaluated the integration between the graft and aortic wall histologically and mechanically in canine models. METHODS: The tissue-engineered vascular graft was woven to be partially degradable with a double-layered fiber (core; polyethylene terephthalate [PET], and sheath; polyglycolic acid [PGA]). The mechanical properties of the graft were assessed compared with a thin-walled woven polyester graft (control; 12 mm in diameter, 30 mm long). The stent-grafts, composed of a stainless Z stent (20 mm in diameter, 25 mm long) and a PET/PGA or control graft (n=5 in each group), were implanted in the descending thoracic aorta of mongrel dogs for 2 months. We assessed the histologic findings of the explants and the degree of adhesion between the graft and aortic wall. RESULTS: The PET/PGA graft achieved nearly the same mechanical properties as those of the control graft in tensile strength and flexibility, with slightly greater water permeability. At 2 months after implantation, in the PET/PGA group, the PGA component had degraded and been replaced by host tissue that contained a mixture of α-smooth muscle actin-positive cells and other host cells. The graft was a unified structure with the aorta. The adhesion strength between the graft and aortic wall was significantly enhanced in the PET/PGA group. CONCLUSIONS: The PET/PGA stent-graft demonstrated histologic and mechanical integration with the native aorta. This next-generation stent-graft might reduce the risk of migration and endoleaks, leading to preferable long-term results of endovascular aneurysm repair.

In situ tissue regeneration using a novel tissue-engineered, small-caliber vascular graft without cell seeding.

OBJECTIVE: Various types of natural and synthetic scaffolds with arterial tissue cells or differentiated stem cells have recently attracted interest as potential small-caliber vascular grafts. It was thought that the synthetic graft with the potential to promote autologous tissue regeneration without any seeding would be more practical than a seeded graft. In this study, we investigated in situ tissue regeneration in small-diameter arteries using a novel tissue-engineered biodegradable vascular graft that did not require ex vivo cell seeding. METHODS: Small-caliber vascular grafts (4 mm in diameter) were fabricated by compounding a collagen microsponge with a biodegradable woven polymer tube that was constructed in a plain weave pattern with a double layer of polyglycolic acid (core) and poly-L-lactic acid (sheath) fibers. We implanted these tissue-engineered vascular grafts bilaterally into the carotid arteries of mongrel dogs (body weight, 20-25 kg). No anticoagulation regimen was used after implantation. We sacrificed the dogs 2, 4, 6, and 12 months (n = 4 in each group) after implantation and evaluated the explants histologically and biochemically. RESULTS: All of the tissue-engineered vascular grafts were patent with no signs of thrombosis or aneurysm at any time. Histologic and biochemical examinations showed excellent in situ tissue regeneration with an endothelial cell monolayer, smooth muscle cells, and a reconstructed vessel wall with elastin and collagen fibers. CONCLUSION: Our study indicated that this novel tissue-engineered vascular graft promoted in situ tissue regeneration and did not require ex vivo cell seeding, thereby conferring better patency on small-caliber vascular prostheses.

Hydrodynamically stable adhesion of endothelial cells onto a polypropylene hollow fiber membrane by modification with adhesive protein.

The effect on the adhesion of endothelial cells of immobilization of adhesion proteins onto a microporous polypropylene hollow fiber membrane for a conventional artificial lung was investigated with the aim of constructing a hybrid artificial lung bearing endothelial cells on the modified membrane. The membrane was modified by adsorption or covalent bonding of adhesion proteins of fibronectin, gelatin, or Pronectin. The density of adherent cells on the membrane modified by adsorption of or covalent bonding with fibronectin reached 1 x 10(5) cells/cm(2) after 1 day of incubation, which corresponds to the confluent cell density in a conventional culture dish, while the cell densities on the membranes modifieds with gelatin and Pronectin were 1-5 x 10(4) cells/cm(2) and 0.5-1 x 10(4) cells/cm(2), respectively. The loading of hydrodynamic shear force (0.23 N/m(2)) for 30 min to the membranes bearing endothelial cells had little effect on the density of adhered cells. The membrane covalently bonded with fibronectin could well maintain a high cell density even after the loading of a higher shear force of 1.15 N/m(2) for 180 min, however, at this level of shear force 49% of adhered cells on the fibronectin-adsorbed membrane were lost after 30 min. A partial cardiopulmonary bypass in rats employing the hybrid artificial lung model composed of a polypropylene hollow fiber membrane covalently bonded with fibronectin and endothelial cell adhesion showed the inhibition of tumor necrosis factor-Alpha release and an increase in IL-10 concentration in the circulating blood compared with that employing an artificial lung without cells. Long-term partial cardiopulmonary bypass employing the hybrid artificial lung model should be studied further.