There is a crucial need for alternatives to native vein or artery for vascular surgery. The clinical efficacy of synthetic, allogeneic or xenogeneic vessels has been limited by thrombosis, rejection, chronic inflammation and poor mechanical properties. Using adult human fibroblasts extracted from skin biopsies harvested from individuals with advanced cardiovascular disease, we constructed tissue-engineered blood vessels (TEBVs) that serve as arterial bypass grafts in long-term animal models. These TEBVs have mechanical properties similar to human blood vessels, without relying upon synthetic or exogenous scaffolding. The TEBVs are antithrombogenic and mechanically stable for 8 months in vivo. Histological analysis showed complete tissue integration and formation of vasa vasorum. The endothelium was confluent and positive for von Willebrand factor. A smooth muscle-specific alpha-actin-positive cell population developed within the TEBV, suggesting regeneration of a vascular media. Electron microscopy showed an endothelial basement membrane, elastogenesis and a complex collagen network. These results indicate that a completely biological and clinically relevant TEBV can be assembled exclusively from an individual's own cells.

We have previously reported initial clinical feasibility with our small diameter tissue engineered blood vessel (TEBV). Here we present in vitro results of the mechanical properties of the TEBVs of the first 25 patients enrolled in an arterio-venous (A-V) shunt safety trial, and compare these properties with those of risk-matched human vein and artery. TEBV average burst pressures (3,490 +/− 892 mmHg, n=230) were higher than native saphenous vein (SV) (1,599 +/− 877 mmHg, n=7), and not significantly different than native internal mammary artery (IMA) (3,196 +/− 1,264 mmHg, n=16). Suture retention strength for the TEBVs (152 +/− 50 gmf) was also not significantly different than IMA (138 +/− 50 gmf). Compliance for the TEBVs prior to implantation (3.4 +/− 1.6 %/100 mmHg) was lower than IMA (11.5 +/− 3.9 %/100 mmHg). By 6 months post-implant, the TEBV compliance (8.8 +/− 4.2 %/100 mmHg, n=5) had increased to values comparable to IMA, and showed no evidence of dilation or aneurysm formation. With clinical time points beyond 21 months as an A-V shunt without intervention, the mechanical tests and subsequent lot release criteria reported here would seem appropriate minimum standards for clinical use of tissue engineered vessels.

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There is a considerable clinical need for alternatives to the autologous vein and artery tissues used for vascular reconstructive surgeries such as CABG, lower limb bypass, arteriovenous shunts and repair of congenital defects to the pulmonary outflow tract. So far, synthetic materials have not matched the efficacy of native tissues, particularly in small diameter applications. The development of cardiovascular tissue engineering introduced the possibility of a living, biological graft that might mimic the functional properties of native vessels. While academic research in the field of tissue engineering in general has been active, as yet there has been no clear example of clinical and commercial success. The recent transition of cell-based therapies from experimental to clinical use has, however, reinvigorated the field of cardiovascular tissue engineering. Here, we discuss the most promising approaches specific to tissue-engineered blood vessels and briefly introduce our recent clinical results. The unique regulatory, reimbursement and production challenges facing personalized medicine are also discussed.