Editors' ChoiceTissue Engineering

Engineering Blood Vessels Through Geometry

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Science Translational Medicine  15 May 2013:
Vol. 5, Issue 185, pp. 185ec80
DOI: 10.1126/scitranslmed.3006519

Many believe that although the 20th century was the century of physics, the 21st century will be remembered by breakthroughs in biology. One of the most exciting of these biological advances is the possibility of engineering spare body parts on demand. If successful, shortage in organ donations and long patient waiting lists would become a thing of the past. Early successes in tissue engineering by the pioneers in the field, however, were hampered by poor patency after implantation. Vascularization and integration with host tissue have been proven essential to ensure survival of engineered tissues after implantation. Indeed, these issues continue to be the major roadblocks to implantation of tissues in humans. Now, Barnanski et al. have used microtissue molding to generate cords of endothelial cells to pursue an alternative solution.

In their approach, a simple twist is introduced to answer an old question: “Does tissue architecture need to be recapitulated in order to ensure function?” They suspended a mix of endothelial cells (ECs) and mesenchymal cells in a collagen type I solution and then inserted the mix in a parallel array of 150-μm-wide channels. In 4 hours, the ECs self-assembled within the microchannels to form cords, whereas mesenchymal cells remained randomly distributed within the collagen matrix. The cell-seeded construct was then peeled off the mold, further embedded in fibrin, and implanted in athymic mice for up to 28 days. The initial large vessels observed 3 and 5 days after implantation within the engineered scaffold already revealed presence of blood and smooth-muscle cells. After 7 days, and sustained after 28 days in vivo, the large vessels remodeled into smaller and more stable capillaries made of a mixture of both graft and host endothelial cells. Most excitingly, coimplantation of EC microchannels with human hepatocytes showed improved function of hepatic tissue. Thus, architecture matters when it comes to engineering functional microvasculature. With this study, the gap between lab and clinic for engineered constructs is only becoming narrower.

J. D. Barnanski et al., Geometric control of vascular networks to enhance engineered tissue integration and function. Proc. Natl. Acad. Sci. U.S.A., published online 22 April 2013 (10.1073/pnas.1217796110). [Abstract]

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