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 At 2 months after implantation, in the PET/PGA group, the PGA component had degraded and been replaced by host tissue that contained a mixture of α-smooth muscle actin-positive cells and other host cells.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.

Newly developed tissue-engineered material for reconstruction of vascular wall without cell seeding.

BACKGROUND: We have developed a tissue-engineered patch for cardiovascular repair. Tissue-engineered patches facilitated site-specific in situ recellularization and required no pretreatment with cell seeding. This study evaluated the patches implanted into canine pulmonary arteries. METHODS: Tissue-engineered patches are biodegradable sheets woven with double-layer fibers. The fiber is composed of polyglycolic acid and poly-L-lactic acid, and compounding collagen microsponges. The patches (20- x 25-mm) were implanted into the canine pulmonary arterial trunks. At 1, 2, and 6 months after implantation (n = 4), they were explanted and characterized by histologic and biochemical analyses. Commercially available patches served as the control. No anticoagulant therapy was administered postoperatively. RESULTS: No aneurysm or thrombus was present within the patch area in all groups. The remodeled tissue predominantly consisted of elastic and collagen fibers, and the endoluminal surface was covered with a monolayer of endothelial cells and multilayers of smooth muscle cells beneath the endothelial layer. The elastic and collagen fibers and smooth muscle cells kept increasing with a maximum at 6 months, while a monolayer of endothelial cells was preserved. The expression levels of messenger RNA of several growth factors in the tissue-engineered patches were higher than those of native tissue at 1 and 2 months and decreased to normal level at 6 months. No regenerated tissue was found on the endoluminal surface in the control group. CONCLUSIONS: The novel tissue-engineered patches showed in situ repopulation of host cells without prior ex vivo cell seeding. This is promising material for repair of the cardiovascular system.

A self-renewing, tissue-engineered vascular graft for arterial reconstruction.

OBJECTIVE: Various tissue-engineered vascular grafts have been studied to overcome the clinical disadvantages of conventional prostheses. Previous tissue-engineered vascular grafts have generally required preoperative cellular manipulation or use of bioreactors to improve performance, and their mechanical properties have been insufficient. We focused on the concept of in situ cellularization and developed a tissue-engineered vascular graft for arterial reconstruction that would facilitate renewal of autologous tissue without any pretreatment. METHODS: The graft comprised an interior of knitted polyglycolic acid compounded with collagen to supply a scaffold for tissue growth and an exterior of woven poly-L-lactic acid for reinforcement. All components were biocompatible and biodegradable, with excellent cellular affinity. The grafts, measuring 10 mm in internal diameter and 30 mm in length, were implanted into porcine aortas, and their utility was evaluated to 12 months after grafting. RESULTS: All explants were patent throughout the observation period, with no sign of thrombus formation or aneurysmal change. Presence in the neomedia of endothelialization with proper integrity and parallel accumulation of functioning smooth muscle cells, which responded to vasoreactive agents, was confirmed in an early phase after implantation. Sufficient collagen synthesis and lack of elastin were quantitatively demonstrated. Dynamic assessment and long-term results of the in vivo study indicated adequate durability of the implants. CONCLUSION: The graft showed morphologic evidence of good in situ cellularization, satisfactory durability to withstand arterial pressure for 12 postoperative months, and the potential to acquire physiologic vasomotor responsiveness. These results suggest that our tissue-engineered vascular graft shows promise as an arterial conduit prosthesis.

Novel tissue-engineered biodegradable material for reconstruction of vascular wall.

BACKGROUND: To solve several problems with artificial grafts, we sought to develop a novel bioengineered material that can promote tissue regeneration without ex vivo cell seeding and that has sufficient durability to be used for artery reconstruction. Here, we tested whether this biodegradable material could accelerate the in situ regeneration of autologous cardiovascular tissue, especially of the arterial wall, in various models of cardiovascular surgeries. METHODS: The tissue-engineered patch was fabricated by compounding a collagen-microsponge with a biodegradable polymeric scaffold composed of polyglycolic acid knitted mesh, reinforced on the outside with woven polylactic acid. Tissue-engineered patches without precellularization were grafted into the porcine descending aorta (n = 5), the porcine pulmonary arterial trunk (n = 8), or the canine right ventricular outflow tract (as the large graft model; n = 4). Histologic and biochemical assessments were performed 1, 2, and 6 months after the implantation. RESULTS: There was no thrombus formation in any animal. Two months after grafting, all the grafts showed good in situ cellularization by hematoxylin/eosin and immunostaining. The quantification of the cell population by polymerase chain reaction showed a large number of endothelial and smooth muscle cells 2 months after implantation. In the large graft model, the architecture of the patch was similar to that of native tissue 6 months after implantation. CONCLUSIONS: A tissue-engineered patch made of our biodegradable polymer and collagen-microsponge provided good in situ regeneration at both the venous and arterial wall, suggesting that this patch can be used as a novel surgical material for the repair of the cardiovascular system.