The prospect of science providing artificial replacements for damaged or diseased body parts is promising, yet replicating organs and tissues in a laboratory setting remains challenging. This is particularly true for blood vessels, which include microscopic, thread-like capillaries measuring as small as 0.005 millimeters—34 times thinner than a human hair—and allowing blood cells to pass one at a time.
A team of researchers from MIT has published a study in PNAS presenting a method to engineer blood vessels in the lab with unprecedented precision. Ensuring the proper formation of blood vessels and thus blood flow is essential for the viability of lab-grown organs or tissues, as capillaries deliver oxygen and nutrients to the tissue.
The innovative approach utilizes magnetic forces to gently stretch and position blood vessel cells. “Healthy tissues depend on organized blood vessel networks, but state-of-the-art protocols don’t enable fabricating such networks within engineered tissues,” explains mechanical engineer Ritu Raman from MIT. “The ability to program blood vessel growth with physical cues may enable reproducible and scalable fabrication of engineered tissues that can be implanted in the body to restore function after debilitating disease or injury.”
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The system involves a small chip containing lab-grown endothelial cells, which line blood vessels, suspended in a collagen gel—an essential protein in the body. A tiny magnet within the chip is manipulated by several external magnets, allowing researchers to guide the growth of new blood vessels by adjusting the magnetic force.
This method is an adaptation of techniques previously used to create artificial muscles and nerves. By varying the external magnetic strength, researchers could control the length and number of new vessels. Although this research is still in an early prototype stage, the initial findings are encouraging.
“The main takeaway is: Stretching the blood vessel back and forth seems to enhance the number of new capillaries that grow,” adds Raman. “Mechanical forces play an important role in our bodies. That means that if you want to grow more or less vessels, or shorter or longer vessels, or vessels in certain directions, we now know how to do that.”
The process of forming new blood vessels, known as angiogenesis, has historically been difficult to replicate with precision. Current methods include 3D printing or growing vessels from individual cells in nutrient-rich dishes, but more precise techniques are needed.
“You can try to pattern chemical cues, like growth factors, to direct where vessels grow, but you can’t do this very precisely,” says Raman. “We thus need other types of patternable cues that can help us build tissues with organized vessels.”
The research team explored the mechanisms behind this process by using cells genetically modified to lack the PIEZO1 gene, which controls ion channels that respond to mechanical pressure. With PIEZO1 inactive, fewer blood vessels formed, underscoring the gene’s importance in vessel development.
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The subsequent steps involve testing how effectively blood circulates through the newly created vessels and integrating these structures into lab-grown tissues and organs, starting with muscle. “We are now investigating how precisely patterning blood vessel growth can help improve muscle function,” says biomedical engineer Jessica Shah from MIT.
The research has been published in PNAS.
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