Date Published: June 26, 2019
Publisher: Public Library of Science
Author(s): Robert Dalton Chavez, Sara Leifer Walls, Kristen O’Halloran Cardinal, Aloke Finn.
Intravascular stents are commonly used to treat occluded arteries during coronary heart disease. After coronary stent implantation, endothelial cells grow over the stent, which is referred to as re-endothelialization. Re-endothelialization prevents blood from clotting on the stent surface and is a good predictor of stent success. Blood vessel mimics (BVMs) are in vitro tissue-engineered models of human blood vessels that may be used to preclinically test stents for re-endothelialization. BVMs have been developed in straight geometries. However, the United States Food and Drug Administration recommends that devices intended to treat coronary occlusions be preclinically tested in bent and bifurcated vessels due to the complex geometries of native coronary arteries. The main objectives of this study were to develop and characterize BVMs in complex geometries.
Bioreactors were designed and constructed so that BVMs could be cultivated in bent (>45°) and bifurcated geometries. Human umbilical vein endothelial cells were sodded onto complex-shaped scaffolds, and the resulting BVMs were characterized for cell deposition. For a final proof of concept, a coronary stent was deployed in a severely angulated BVM.
The new bioreactors were easy to use and mounting scaffolds in complex geometries in the bioreactors was successful. After sodding scaffolds with cells, there were no statistically significant differences between the cell densities along the length of the BVMs, on the top and bottom halves of the BVMs, or on the inner and outer halves of the BVMs. This suggests cells deposited evenly throughout the scaffolds, resulting in consistent complex-geometry BVMs. Also, a coronary stent was successfully deployed in a severely angulated BVM.
Bioreactors can be constructed for housing complex-shaped vessels. BVMs can be developed in the complex geometries observed in native coronary arteries with endothelial cells evenly dispersed throughout BVM lumens.
Coronary heart disease (CHD), which is the leading cause of death in the United States , occurs when plaque occludes coronary arteries. Coronary occlusions can be treated with stents . Stents are latticed tubes that can be crimped onto catheters and deployed at blockage sites . During stent deployment, stents denude endothelial cells from vessel walls, but eventually a new endothelial lining grows over the stented region [4,5]. This re-growth is known as re-endothelialization and is important for successful healing after stent implantation. A confluent monolayer of endothelial cells modulates local hemostasis and thrombolysis and protects vascular smooth muscle cells from circulating growth-promoting factors .
In the present study, we designed and constructed new BVM bioreactors with off-the-shelf, easy-to-use components, eliminating the difficult aspects of previous designs and allowing cultivation of BVMs in a range of vessel geometries. A multifunctional system was designed and fabricated, reducing the overall number of bioreactors. Closing off unused inlets or outlets with luer caps when inserting various scaffold geometries was easy. Overall, the multifunctional bioreactors streamlined development of complex-shaped BVMs.