MIT scientists develop a new way to grow artificial blood vessels

Artificial tissues can mimic muscle, liver, kidney and skin, but they still face a basic survival problem: cells need blood vessels. Without a dense vascular network, oxygen and nutrients cannot reach deep into engineered tissue, and waste cannot escape.MIT engineers have now shown that mechanical stretching can help solve that problem. By repeatedly pulling on a lab-grown vessel, they increased the growth of new capillary-like sprouts and guided the direction those sprouts followed.The work, reported in the Proceedings of the National Academy of Sciences, introduces a vessel-on-a-chip platform that uses magnets to apply controlled strain inside a three-dimensional tissue model. The system lets researchers adjust how strongly, how often and in which direction a vessel is stretched.“Healthy tissues depend on organized blood vessel networks, but state-of-the-art protocols don't enable fabricating such networks within engineered tissues,” said Ritu Raman, an associate professor of mechanical engineering at MIT and the study’s co-lead author. “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.”A vessel that responds to exerciseThe device is smaller than a postage stamp. It contains a central hollow channel lined with human endothelial cells, which naturally form blood vessels. The channel sits inside a collagen gel that also holds a small magnetic actuator.An external magnet moves the embedded actuator, pulling the surrounding gel and stretching the vessel wall. A motorized three-axis system controls the magnet’s distance, speed, direction and frequency.The endothelial cells formed a complete vessel lining within 48 hours. The resulting channel measured about 604 micrometers across and could carry fluid. Within three days, new sprouts began extending into the surrounding gel.The team then applied either 5 percent or 15 percent strain. Some vessels received dynamic stretching at one cycle per second, while others experienced static strain. Stimulation lasted one hour per day for three days.“The main takeaway is: Stretching the blood vessel back and forth seems to enhance the number of new capillaries that grow,” Raman said.All forms of mechanical stimulation increased total sprouting compared with unstimulated vessels. Yet the strain level changed the pattern of growth.Five percent dynamic strain produced the largest number of sprouts. Fifteen percent dynamic strain produced fewer sprouts, but those vessels grew longer. The sprouts remained within a capillary-scale size range that conventional 3D bioprinting struggles to reproduce.Mechanical cues steer growing vesselsDirection mattered as much as strength. When the team stretched the gel along one axis, sprouts preferentially grew along that same line.At 5 percent strain, sprouting along the actuation axis increased threefold compared with unstimulated controls. At 15 percent strain, it rose 2.4-fold.The researchers then changed the direction of stimulation after three days. Some vessels were first stretched along the x-axis and later along the y-axis. Others were redirected upward along the z-axis.The growing vessels adjusted their paths. Some formed L-shaped structures after the direction changed. About 67 percent of sprouts reoriented during x-to-y stimulation, while 71 percent reoriented during x-to-z stimulation.The change did not erase earlier growth. Instead, sprouts continued extending along the newly imposed direction.“We’re finding that moving is good, which is always the takeaway of everything we do in our lab,” Raman said. “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.”New sprouts carried fluidThe team tested whether the sprouts were more than simple cellular projections. Fluorescent tracers introduced into the main channel moved into connected sprouts, showing that part of the new network contained hollow lumens capable of carrying fluid.Mechanical stimulation also improved the barrier formed by the vessel wall. Permeability to a small fluorescent tracer fell by nearly half across stimulated conditions. Permeability to a larger tracer dropped by about one-third.The direction of stimulation did not significantly change barrier function. That suggests the researchers could redirect growth without weakening the vessel wall.Tests also ruled out two alternative explanations. Added vascular endothelial growth factor, or VEGF, was not required for the strain response. Exposure to the magnetic field alone did not significantly change sprouting or permeability.PIEZO1 helps cells sense the pullTo understand how cells detected the force, the team examined PIEZO1, a gene that controls a pressure-sensitive ion channel in cell membranes.These channels open in response to mechanical pressure and allow ions to pass through the membrane. That activity can trigger changes in cell behavior.The researchers used gene editing to suppress PIEZO1 in the endothelial cells. Under normal conditions, 15 percent dynamic strain increased total sprouting by 1.6-fold. With PIEZO1 suppressed, the increase fell to 1.1-fold.The result shows that PIEZO1 contributes to strain-induced vessel growth. However, barrier strengthening remained intact after the gene was suppressed, indicating that other force-sensing pathways likely control that response.RNA sequencing supported a broader mechanical response. Dynamic strain altered hundreds of genes and increased activity in pathways tied to angiogenesis, cell migration, adhesion and shape. Genes associated with permeability, cell death and vessel regression were reduced.The model still has important limits. It contains only endothelial cells and does not include smooth muscle cells, pericytes or fibroblasts. The experiments also lacked continuous blood flow, allowing the team to isolate the effects of mechanical strain.Practical implications of the researchPrecisely guiding small blood vessels could remove one of the main barriers in tissue engineering. Existing methods can print large channels or encourage cells to self-organize, but they struggle to create fine networks with controlled geometry.This magnetic platform offers a way to add physical instructions after tissue growth has begun. Researchers can change strain direction over time and guide vessels through three dimensions without relying only on chemical gradients.Future versions will need additional cell types and flowing blood to better reproduce native circulation. The team is now investigating whether mechanically patterned vessels can improve engineered muscle function.If the approach remains effective in more complex tissues, it could help scientists build thicker, better supplied implants. It may also support more realistic laboratory models for studying diseases involving abnormal blood vessel growth.Research findings are available online in the journal PNAS.The original story "MIT scientists develop a new way to grow artificial blood vessels" is published in The Brighter Side of News.Related StoriesLike these kind of feel good stories? Get The Brighter Side of News' newsletter.