Although future scientific breakthroughs may one day allow damaged or diseased body parts to be replaced with artificial implants, growing organs and tissues in a laboratory setting remains an exceptionally difficult challenge.
This is particularly true for the creation of intricate vascular networks, as their structure becomes incredibly delicate at the microscopic level of capillaries. These capillaries can measure just 0.005 millimeters in diameter—34 times thinner than a human hair—and allow red blood cells to pass through only one at a time.
Researchers from the Massachusetts Institute of Technology have published a study in the journal PNAS that details a method for creating blood vessels in the lab with significantly greater precision than previously possible.
Proper blood vessel formation—and consequently, blood flow—is critical for the success of any lab-grown organ or tissue, as tiny capillaries supply the tissue with blood, delivering oxygen and nutrients.
This new approach leverages magnetic forces that gently stretch and pull blood vessel cells, positioning them correctly.
“Healthy tissues rely on organized networks of blood vessels, but current protocols do not allow us to build such networks inside engineered tissues,” says Ritu Raman from MIT. “The ability to program blood vessel growth using physical cues could enable the reproducible and scalable creation of engineered tissues that can be implanted into the body to restore function after severe illness or injury.”
The system is based on a small chip containing endothelial cells (the cells that line blood vessels), which are grown in the lab and embedded in a collagen gel—a protein that serves as one of the body’s most essential building blocks.
A tiny magnet was also placed inside the chip, which was then controlled by several external magnets operating in three dimensions. By adjusting the force applied to the chip’s magnet, the researchers could determine how new blood vessels would grow.
This is an adapted version of the same approach the researchers previously used to create artificial muscles and nerves.
By altering the strength of the external magnetic pull, the researchers were also able to control the length and number of new vessels that emerged. We are still in an early, prototype stage, but the initial results are promising.
“The key finding is that stretching the blood vessel forward and backward appears to increase the number of new capillaries formed,” says Raman. “Mechanical forces play a significant role in our bodies. This means that if we want to increase or decrease the number of blood vessels, make them shorter or longer, or direct them in a specific direction, we now know how to do it.”
From a technical standpoint, the formation of new blood vessels is called angiogenesis, but previous methods for artificially recreating it did not provide sufficient control.
Currently, blood vessels can be 3D-printed or grown from individual cells in Petri dishes filled with nutrients and other chemical compounds, but scientists are seeking a method that offers greater precision.
“You can try to guide chemical signals, like growth factors, to determine where vessels will grow, but doing this with high precision is impossible,” says Raman. “So, we need other types of structured signals to help us create tissues with an organized circulatory system.”
The research team also investigated the underlying mechanisms. They repeated their experiments using cells that were genetically modified to function without the PIEZO1 gene.
This gene controls ‘cellular gatekeepers’—ion channels responsible for regulating what enters and exits the cell, in this case, a specific type of channel that responds to mechanical pressure. When the PIEZO1 gene was turned off, fewer blood vessels formed, demonstrating how crucial the activation of these ion channels is.
The next steps involve testing how well blood actually flows through the arteries, veins, and capillaries created with the chip, as well as to the lab-grown organs and tissues surrounding the blood cell structure, starting with muscle.
“We are now investigating how precisely regulating blood vessel growth can help improve muscle function,” summarizes Jessica Shah from MIT.
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