Mechanical properties of completely autologous human tissue engineered blood vessels compared to human saphenous vein and mammary artery

Abstract

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.

Generation, Endothelialization, and Microsurgical Suture Anastomosis of Strong 1-mm-Diameter Collagen Tubes

“…On the other hand, dried-and-crosslinked collagen tubes yielded average burst pressures of *1300 mm Hg, which is comparable to the value obtained by Chaikof and coworkers for tubes of 1.3 mm inner diameter. 18 While this value is still shy of the burst pressure of native arteries (which can be as high as 3000 mm Hg) 25 , it is close to the value for native vein (*1200 mm Hg) 26 and more than sufficient to withstand pressure of arterial flow. Compliance of dried-andcrosslinked tubes averaged *1.7%/100 mm Hg, which is comparable to the value (0.7-2.6%/100 mm Hg) of mammalian vein.…”

Expression of Versican Isoform V3 in the Absence of Ascorbate Improves Elastogenesis in Engineered Vascular Constructs

“…In addition, limitation of exposure to ascorbate significantly improved the structural and biomechanical properties of the constructs. While the constructs described here do not meet the threshold of burst strength considered desirable for safe implantation in vivo, 47,48 the use of V3-overexpressing ASMCs and limitation of ascorbate may ultimately improve the performance of TEBVs through provision of a stronger, more elastic vascular media. Potentially, by combining engineered media populated with ASMCs with mechanically strong, fibroblast-based engineered adventitial layers (fibroblastic constructs have recently shown promising results as vascular grafts in humans 3 ), a highly functional human TEBV could be produced.…”

Bioengineered blood vessels

“…Several criteria are used to determine TEBV function: i) mechanical compatibility, including elasticity, suture retention, burst pressure and compliance, to ensure graft endurance of dynamic changes, while avoiding mechanical mismatch that could lead to graft failure [72,73]; ii) cell distribution to achieve a monolayer of EC in the intimal layer, SMC in the medial layer [60] and FB in the adventitial layer, as well as appropriate cellular response to external stimulation [64,74]; iii) functional compatibility, including patency and flow profile to avoid hyperplasia, aneurism or plaque formation after implantation [31,44,75]. The maturation of TEBV in vivo is a complex process that requires a set of chemical and physical stimulations to control scaffold degradation and reorganization of ECs and SMCs [76,77].…”