Conference Report - Stem Cells and Tissue Engineering -- Dreaming Things That Never Were

Bioengineering Tissues to Bypass Grafts

Vascular surgeons achieve the replacement of blood vessels with autologous tissues regrafted to damaged sites or synthetic materials. Replacements are therefore often limited to vessels with a diameter > 6 mm, and they are not available for about one third of the patients who need one.

Challenges in designing new vascular replacements are the risk of thrombogenicity and occlusion, related to the lack of endothelium, and the difficulty to achieve suitable mechanical properties. Most experimental replacements undergo bust failure because of the low density of the matrixes and the insufficient degree of crosslinking achieved in the constructs.

As illustrated by Dr. Jennifer West^[15] of Rice University, Houston, Texas, a number of factors may contribute to the success or failure of an experimental vascular replacement: the cell source, genetic makeup of the cell itself, choice of scaffold material, presence of bioactive factors, and mechanic conditions.^[16]

For example, transfection of smooth muscle cells (SMCs) with the nitric oxidase enzyme reduced adhesion of platelets and thus decreased thrombogenicity.^[17] Expression of lysyl oxidase, on the other hand, was found to increase the mechanical properties.^[18] Collagen gels seeded with SMCs expressing lysyl oxidase showed an increase in elasticity and tensile strength.

The material(s) used to build a scaffold should:

The polymers used may be synthetic (eg, polyesters) or of natural origin (eg, collagen gels). Although synthetic polymers offer better control, greater safety, and easier processing, natural polymers allow better tissue formation. The polymers, in fact, support the tissue while it is forming, promoting adhesion of the desired cells, avoiding attachment of undesired cells, and overall favoring cell migration.

A new polymer, poly(ethylene glycol) diacrylate, is being evaluated as a bioactive scaffold built through photopolymerization. Poly(ethylene glycol) units are added to the scaffold under construction and polymerized by exposure to ultraviolet light to build the main frame. Collagenase or elastase-degradable peptides can also be added to target the scaffold for degradation by specific proteolytic enzymes.^[16]

The addition of biospecific cell-adhesion molecules (REDV for endothelial cells and RGDS, more ubiquitous) ensures interaction with specific receptors and the incorporation of specific ligands or cell types -- eg, adhesion of SMCs to an RGDS hydrogel.^[19]

Migration of endothelial cells or fibroblasts through a collagen-mimetic hydrogel can by measured with a transwell assay, with the determination of a migration index. The extent of cell migration can be enhanced adding tethered molecules of epidermal growth factor, whereas increased deposits of extracellular matrix may be achieved by the addition of interspersed molecules of transforming growth factor-beta.^[20]

To engineer a vascular graft, an annular mold is filled and exposed to ultraviolet light to obtain a solid structure. A suspension of endothelial cells in polymer solution contributes to the formation of the intimal layer upon interfacial polymerization. The construct is then passed in a bioreactor chamber to allow for a greater cell proliferation and exposure to sheer stress. The mechanical conditioning achieved in the bioreactor, in fact, improves the mechanical properties of the bioengineered vessel.

As noted by Dr. West, such a procedure is more easily applicable to the preparation of microvessels, but its use may be feasible also for larger vascular structures.^[15]

© 2004 Medscape

Cite this: Conference Report - Stem Cells and Tissue Engineering -- Dreaming Things That Never Were - Medscape - Aug 02, 2004.