|Research| Project 1

Research Project 1:

Tissue engineering of small diameter arteries (funded by NIH, AHA, and NSF)

We are engineering small diameter arteries from synthetic scaffolds and primary vascular cells. We use seamless tubular scaffolds made of a biodegradable elastomer, poly(glycerol sebacate). The scaffolds have a range of pore sizes that facilitate cell seeding and proliferation during pulsatile perfusion of the developing constructs. We use cells from 4-year-old baboons to parallel the potential outcomes from human cells. The scaffolds are initially cultured with smooth muscle cells to mimic the tunica media, and they are later cultured with circulating endothelial progenitor cells isolated from peripheral blood to mimic the tunica intima. These constructs produce extracellular matrix that contains elastin and collagen, both necessary for the unique mechanical behavior of native arteries. Elastin is rarely expressed by cells in vitro. Unlike previous successes of in vitro elastin expression, our strategy does not rely on genetic manipulation or large amounts of growth factors. Mechanical testing has shown that the engineered arteries possess compliance (an elastic and reversible change in shape) similar to native arteries. Eight-week culture is sufficient for these arteries to exhibit burst pressures as high as human diastolic pressure in the systemic circulation. We are working on detailed characterization and optimization of the constructs with the ultimate goal of a clinically-relevant GMP procedure and product.

Related publications:

1. Gao, J.; Crapo, P. M.; Wang, Y. Macroporous Elastomeric Scaffolds with Extensive Micropores for Soft Tissue Engineering. Tissue Eng., 12: 917-925, 2006.

2. Sales, V. L.; Engelmayr, G. C., Jr.; Johnson, J. A., Jr.; Gao, J.; Wang, Y.; Sacks, M. S.; Mayer, J. E., Jr. Protein Pre-Coating of Elastomeric Tissue-Engineering Scaffolds Increased Cellularity, Enhanced Extracellular Matrix Protein Production, and Differentially Regulated the Phenotypes of Circulating Endothelial Progenitor Cells. Circ. In press.

3. Crapo, P. M.; Gao, J.; Wang, Y. Seamless Tubular Poly(glycerol sebacate) Scaffolds: High-yield Fabrication and Potential Applications. J. Biomed. Mat. Res. In press.