MIT scientists have developed a groundbreaking method to grow artificial blood vessels, marking a significant advancement in the field of tissue engineering. This innovative approach involves using mechanical stretching to enhance the growth of new capillary-like sprouts and guide their direction, offering a promising solution to a fundamental challenge in artificial tissue development. The research, published in the Proceedings of the National Academy of Sciences, introduces a vessel-on-a-chip platform that utilizes magnets to apply controlled strain within a three-dimensional tissue model, allowing researchers to adjust the intensity, frequency, and direction of stretching. This level of control is crucial for fabricating organized blood vessel networks within engineered tissues, a feat that has eluded previous methods.
The device, smaller than a postage stamp, features a central hollow channel lined with human endothelial cells, which naturally form blood vessels. These cells, along with a collagen gel, create a complete vessel lining within 48 hours, capable of carrying fluid. The team then applied various levels of strain (5% and 15%) and different types of mechanical stimulation (dynamic and static) to observe the effects on vessel growth and permeability.
The findings reveal that stretching the blood vessel back and forth significantly enhances the number of new capillaries that grow. Interestingly, the level of strain influences the pattern of growth, with 5% dynamic strain producing the largest number of sprouts, while 15% dynamic strain results in fewer sprouts but longer vessels. This discovery highlights the importance of both the strength and direction of mechanical cues in guiding vessel growth.
The researchers also found that the direction of stimulation plays a crucial role, with sprouts preferentially growing along the axis of stretching. By redirecting the direction of stimulation, the team observed that the growing vessels adjusted their paths accordingly, forming L-shaped structures. This adaptability demonstrates the potential for precise control over vessel growth and direction.
Furthermore, the study demonstrates that the new sprouts are more than just cellular projections. Fluorescent tracers introduced into the main channel moved into connected sprouts, indicating the presence of hollow lumens capable of carrying fluid. Mechanical stimulation also improved the barrier function of the vessel wall, reducing permeability to small and large tracers, suggesting that this approach can enhance the overall functionality of artificial vessels.
The underlying mechanism behind this phenomenon involves the PIEZO1 gene, which controls a pressure-sensitive ion channel in cell membranes. Gene editing experiments revealed that PIEZO1 contributes to strain-induced vessel growth, but other force-sensing pathways likely control the barrier strengthening response. RNA sequencing supported a broader mechanical response, showing that dynamic strain alters hundreds of genes and activates pathways related to angiogenesis, cell migration, adhesion, and shape.
While the current model has limitations, including the absence of certain cell types and continuous blood flow, it offers a significant step forward in tissue engineering. The magnetic platform provides a way to add physical instructions after tissue growth has begun, allowing researchers to guide vessels through three dimensions without relying solely on chemical gradients. Future versions of this technology may lead to thicker, better-supplied implants and more realistic laboratory models for studying diseases involving abnormal blood vessel growth.
In conclusion, this research represents a major breakthrough in the field of tissue engineering, offering a novel approach to growing artificial blood vessels. The ability to precisely guide small blood vessels could revolutionize the way we engineer tissues, potentially transforming the treatment of various diseases and advancing our understanding of vascular biology.
