A COMPLETELY BIOLOGICAL TISSUE-ENGINEERED HUMAN BLOOD-VESSEL

Mechanically challenged tissue-engineered organs, such as blood vessel s, traditionally relied on synthetic or modified biological materials for structural support. In this report, we present a novel approach to tissue-engineered blood vessel (TEBV) production that is based exclus ively on the use of cultured human cells, i.e., without any synthetic or exogenous biomaterials. Human vascular smooth muscle cells (SMC) cu ltured with ascorbic acid produced a cohesive cellular sheet. This she et was placed around a tubular support to produce the media of the ves sel. A similar sheet of human fibroblasts was wrapped around the media to provide the adventitia. After maturation, the tubular support was removed and endothelial cells were seeded in the lumen. This TEBV feat ured a well-defined, three-layered organization and numerous extracell ular matrix proteins, including elastin. In this environment, SMC reex pressed desmin, a differentiation marker known to be lost under standa rd culture conditions. The endothelium expressed von Willebrand factor , incorporated acetylated LDL, produced PGI(2), and strongly inhibited platelet adhesion in vitro. The complete vessel had a burst strength over 2000 mmHg. This is the first completely biological TEBV to displa y a burst strength comparable to that of human vessels. Short-term gra fting experiment in a canine model demonstrated good handling and sutu rability characteristics. Taken together, these results suggest that t his novel technique can produce completely biological vessels fulfilli ng the fundamental requirements for grafting: high burst strength, pos itive surgical handling, and a functional endothelium.