Tissue engineering of aortic tissue: dire consequence of suboptimal elastic fiber synthesis in vivo.

OBJECTIVE To study autologous tissue engineered blood vessels (TEBV) in the descending aorta of juvenile sheep. METHODS Autologous vascular smooth muscle cells (vSMC) and endothelial cells were obtained from ovine carotid arteries. vSMC were seeded on bioresorbable scaffolds and dynamically cultured for 14 days. Following endothelialization an additional external ovine small intestinal submucosa wrapping was applied. Constructs were implanted in the descending aorta of juvenile sheep and removed after 1, 3, 6, 12 and 24 weeks for evaluation with histological, microscopical and biochemical techniques. RESULTS Up to 3 months after implantation, grafts were fully patent, without any signs of dilatation, occlusion or intimal thickening. Scanning electron microscopy revealed a confluent luminal endothelial cell layer. In contrast, the 6 months graft displayed significant dilatation and partial thrombus formation. Histology displayed layered tissue formation resembling native aorta. Extracellular matrix (ECM) stains, immunostaining and Transmission Electron Microscopy (TEM) revealed alternating layers of vSMC and extracellular matrix consisting of collagen, elastin and glycosaminogycans. Compared to native aorta, the elastin content of the TE grafts was significantly reduced. CONCLUSION In this study, we report for the first time, the implantation of a TEBV in the descending aorta in a large animal model. TEBV were fully functional for up to 3 months. At 6 months the graft remained functional but significantly dilated, most likely caused by an insufficient elastic fiber synthesis. Hence, future studies need to focus on the stimulation of elastin synthesis in TEBV.