When cardiovascular disease causes blocked blood vessels, tissues die because the oxygen carried by blood cells cannot reach the tissue. Tissue starved of oxygen is called ischemic. Surgery can remove blockages in large vessels in the heart or legs but is not possible in small vessels; they are just too small to manipulate.
To address this problem, researchers funded by the National Institute of Biomedical Imaging and Bioengineering (NIBIB) designed 3D-printed patches seeded with vessel-inducing endothelial cells in various geometric patterns.
Using a mouse model of hindlimb ischemia, the researchers identified specific patch patterns that induced growth of organised, tissue-saving blood vessels, demonstrating the potential for the novel technology to address this significant public health problem.
Ischemic cardiovascular disease is the leading cause of death and disability in the United States and is growing worldwide. Impaired blood circulation to tissues and organs causes many serious conditions including peripheral artery disease, heart failure, and stroke. Much of the damage that causes these conditions occurs in small vessels that are difficult to treat.
Now, an interdisciplinary group of engineers and physicians has teamed up to apply biomedical engineering strategies to address the problem of ischemia caused by small vessel damage. Led by Christopher Chen, M.D., Ph.D., Professor of Biomedical Engineering and Founding Director of the Biological Design Center at Boston University, the results of their work are reported in Nature Biomedical Engineering.
With surgery not possible in small vessels, researchers have turned to strategies to induce the formation of new vessels. These attempt to mimic the body’s natural repair process where vascular endothelial cells and various vascular growth factors can induce the sprouting of new vessels in response to damage. However, using this approach to develop a successful treatment has proven difficult.
“We know that when growth factors are injected into a tissue, they do induce the sprouting of new blood vessels, but in a disorganised pattern unable to deliver oxygen to ischemic tissues” explained Chen. “Our goal was to use engineering to direct the growth of new vessels into an orderly, functional network.”
To direct organised vessel formation, the researchers designed and constructed 3D-printed vascular patches with different patterns of channels. The channels were lined with the endothelial cells that induce the sprouting of new blood vessels.
The patterns included straight, parallel rows of channels, a grid pattern with channels crisscrossing each other, and a “no pattern” control with the endothelial cells scattered randomly over the entire patch.
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Image credit: NIBIB.