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.

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Background: The growing size of the end stage renal disease (ESRD) population highlights the need for effective dialysis access. Exhausted native vascular access options have led to increased use of catheters and prosthetic shunts, which are both associated with high risks of access failure and infection. Emerging alternatives include tissue-engineered vascular grafts (TEVG). Here we present the endpoint results for 10 ESRD patients with the scaffold-free tissue-engineered vascular access produced from sheets of extracellular matrix produced in vitro by human cells in culture. Methods: Grafts were implanted as arteriovenous shunts in 10 ESRD patients with a complex history of access failure. Follow-up included ultrasound control of graft morphology and function, dialysis efficiency, access failure, intervention rate, as well as immunohistochemical analysis of graft structure. Results: One patient died of unrelated causes and three shunts failed to become useable access grafts during the 3-month maturation phase. The 12-month primary and secondary patency for the other six shunts was 86%. Survival of six shunts functioning as the vascular access was 22 ± 12 months with longest primary patency of 38.6 months. The dialysis event rate of 3.34 per patient-year decreased significantly with the use of this TEVG to 0.67. Conclusions: This living autologous tissue-engineered vascular graft seems to be an alternative to synthetic vascular access options, exhibiting advantages of native arteriovenous fistula.