<p class="first" id="d3314164e75">Mechanically challenged tissue-engineered organs,
such as blood vessels, 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 exclusively on the use of cultured human cells, i.e., without any synthetic
or exogenous biomaterials. Human vascular smooth muscle cells (SMC) cultured with
ascorbic acid produced a cohesive cellular sheet. This sheet was placed around a tubular
support to produce the media of the vessel. 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 featured
a well-defined, three-layered organization and numerous extracellular matrix proteins,
including elastin. In this environment, SMC reexpressed desmin, a differentiation
marker known to be lost under standard culture conditions. The endothelium expressed
von Willebrand factor, incorporated acetylated LDL, produced PGI2, 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 display a burst strength comparable
to that of human vessels. Short-term grafting experiment in a canine model demonstrated
good handling and suturability characteristics. Taken together, these results suggest
that this novel technique can produce completely biological vessels fulfilling the
fundamental requirements for grafting: high burst strength, positive surgical handling,
and a functional endothelium.
</p>