Abstract-Although the need for a functional arterial replacement is clear, the lower blood flow velocities of small-diameter arteries like the coronary artery have led to the failure of synthetic materials that are successful for large-diameter grafts. Although autologous vessels remain the standard for small diameter grafts, many patients do not have a vessel suitable for use because of vascular disease, amputation, or previous harvest. As a result, tissue engineering has emerged as a promising approach to address the shortcomings of current therapies. Investigators have explored the use of arterial tissue cells or differentiated stem cells combined with various types of natural and synthetic scaffolds to make tubular constructs and subject them to chemical and/or mechanical stimulation in an attempt to develop a functional small-diameter arterial replacement graft with varying degrees of success. Here, we review the progress in all these major facets of the field. Key Words: tissue engineering Ⅲ artery Ⅲ collagen Ⅲ elastin Ⅲ vascular graft I n 2002, more than 500 000 surgical procedures were performed involving replacement of small-caliber blood vessels. 1 Despite a clear clinical need for a functional arterial graft, success has been limited to arterial replacements of large-caliber vessels such as the thoracic and abdominal aorta, arch vessels, iliac, and common femoral arteries; however, small-caliber (Ͻ6 mm) arterial substitutes, which account for a majority of the demand, have generally proved inadequate largely because of acute thrombogenicity of the graft, anastomotic intimal hyperplasia, aneurysm formation, infection, and progression of atherosclerotic disease. 2 The lower blood flow velocities of smaller vessels pose a different set of design criteria and introduce a host of new problems not encountered in large-caliber arterial substitutes where Dacron and expanded polytetrafluorethylene grafts have succeeded.Although autologous vessels, such as the saphenous vein, remain the standard for small diameter grafts, many patients do not have a vessel suitable for use because of vascular disease, amputation, or previous harvest. Moreover, this method requires a second surgical procedure to obtain the vessel. Tissue engineering has emerged as a promising approach to address the shortcomings of current options. Investigators have explored the use of arterial tissue cells combined with various types of natural and synthetic scaffolds to make tubular constructs and subject them to chemical and/or mechanical stimulation in an attempt to develop a functional small-diameter arterial replacement graft with varying degrees of success. There have been several reviews of vascular tissue engineering studies in recent years. [3][4][5][6] Here, we review the progress in Many design criteria have been proposed for the development of a functional small-diameter arterial replacement graft. 2,5,6,9 -13 It must be biocompatible, ie, nonthrombogenic, nonimmunogenic, and resistant to infection, all of which are associated wi...

A scaleable perfusion bioreactor has been developed for tissue engineering of small diameter arterial constructs. This modular bioreactor allows for dynamic sequential seeding of smooth muscle and endothelial cells, biomechanical stimulation of cells during culture, and monitoring of tissue growth and maturation. Bovine aortic smooth muscle and endothelial cells were seeded onto porous tubular poly(glycolic acid) nonwoven scaffolds and cultured in the bioreactor under pulsatile flow conditions for up to 25 days. Cell proliferation was more than 3-fold after 4 days, smooth muscle cells expressed differentiated phenotype after 16 days, and collagen and elastin were distributed throughout the construct after 25 days of culture. In bioreactor experiments in which the construct lumen was seeded with endothelial cells by perfusion after 13 days of smooth muscle cell culture, endothelial cell seeding efficiency was 100%, and a confluent monolayer was observed in the lumen within 48 h. These data demonstrate that this perfusion bioreactor supports sequential seeding of constructs with smooth muscle and endothelial cells. Dynamic culture under pulsatile flow leads to cellular expression of differentiated function and extracellular matrix deposition toward the development of tissue-engineered arterial constructs.