Sheet‐Based Tissue Engineering: From Bench Top to the First Clinical Use of a Completely Biological Tissue Engineered Blood Vessel

Abstract

The initial vision of Tissue Engineering was to produce living, autologous and completely biological organs for transplant. However, in the case of blood vessels, previous approaches have relied on permanent synthetic scaffolds to provide the requisite mechanical strength. Sheet-Based Tissue Engineering is the first method that allows the in vitro production of mechanically sounds tissues and organs without the need for exogenous scaffolding. Tissue engineered blood vessels (TEBVs) were produced from skin fibroblasts and endothelial cells isolated from older patients suffering from vascular disease and/or diabetes. In animal models, TEBVs showed long-term patency (over 8 months), no mechanical failure and positive histological remodeling. A small clinical trial was initiated to asses the potential of the TEBV as a arteriovenous shunt. At the time of submission, TEBVs produced from the cells of patients (age: 67±11 y, n=6) have all demonstrated satisfactory burst pressures (3658±1074 mmHg), suture retention strength (192±29 gf) and compliance (2.6±0.4 %/100mmHg). First clinical use revealed that these TEBVs can be easily sutured using standard equipment and technique. Grafts showed high flow (>1L/min), no signs of mechanical failure and patency through 6 months (on going). Grafts resisted repeated puncture and could be use for hemodialysis. IVUS studies revealed an almost 3-fold increase in compliance without vessel dilatation. These data demonstrate the feasibility of producing completely biological and autologous TEBVs for arterial bypass from cells of elderly patients in poor health. Partly funded by NIH/NHLBI R44HL64462.