While future scientific advances may enable the replacement of diseased or injured body parts with artificial implants, growing organs and tissues in the laboratory remains an extremely challenging task.
This is particularly true for the creation of branching vascular networks, as their structure becomes incredibly fine at the level of microscopic capillaries. These capillaries can have a diameter of just 0.005 millimeters—34 times thinner than a human hair—and allow red blood cells to pass through only one at a time.
Scientists from the Massachusetts Institute of Technology (MIT) have published a study in the journal PNAS detailing a method for creating blood vessels in the laboratory with significantly greater precision than previously possible.
The proper formation of blood vessels (and, consequently, blood flow) is crucial to the success of any lab-grown organ or tissue, as fine capillaries supply blood to the tissue, delivering oxygen and nutrients.
The new approach relies on magnetic forces that gently stretch and pull blood vessel cells, guiding them into the desired position.
“Healthy tissues depend on organized networks of blood vessels, yet current protocols do not allow for the creation of such networks within engineered tissues,” says Ritu Raman of MIT. “The ability to program blood vessel growth using physical cues could enable the reproducible and scalable creation of artificial tissues that can be implanted into the body to restore function following 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 laboratory and embedded in a collagen gel; collagen is a protein that serves as one of the body’s essential building blocks. A tiny magnet was also embedded within the chip, which was then manipulated in three dimensions by several external magnets. By adjusting the force exerted on the chip’s magnet, the researchers could determine how new blood vessels grew.
This is an adapted version of the same approach researchers previously used to create artificial muscles and nerves.
By varying the strength of the external magnetic pull, the researchers were also able to control the length and number of the emerging new vessels. We are still at an early, prototype stage, but the initial results are promising.
“The main takeaway is that stretching a blood vessel back and forth appears to increase the number of new capillaries that form,” says Raman. “Mechanical forces play a vital 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 guide them in a specific direction, we now know how to do it.”
Technically speaking, the formation of new blood vessels is called angiogenesis, but previous methods for artificially recreating it did not offer 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 way to achieve greater precision.
“You can try directing chemical signals, such as growth factors, to determine where vessels will grow, but doing so with high precision is impossible,” says Raman. “Therefore, we need other types of structured signals to help us create tissues with an organized circulatory system.”
The research team also investigated the mechanisms underlying this process. They repeated their experiments using cells genetically modified to function without the PIEZO1 gene. This gene controls “cellular gatekeepers”—ion channels responsible for regulating what enters and exits the cell; specifically, in this case, a type of channel that responds to mechanical pressure. When the PIEZO1 gene was disabled, fewer blood vessels formed, demonstrating the critical importance of ion channel activation.
The next steps involve assessing how well blood actually flows through the arteries, veins, and capillaries created using the chip, as well as to the lab-grown organs and tissues surrounding the structure.
“We are currently investigating how the precise regulation of blood vessel growth can help improve muscle function,” summarizes Jessica Shah of the Massachusetts Institute of Technology.
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