UC San Diego Breakthrough: 3D Printed Blood Vessel Network Survives and Functions Within Mice

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download-8One of the most difficult roadblocks in the quest to 3D print functional, transplantable human organs isn’t the printing of the organ itself – it’s the creation of the critical network of blood vessels that enable the organ to function within the body. Scientists have been working hard to develop 3D printed blood vessels that are capable of surviving and doing the crucial work of transporting blood, nutrients, waste and other materials throughout the body, but it’s been a difficult slog; most existing methods of 3D printing blood vessels are slow, expensive, and are capable of producing only single blood vessels that can’t be integrated with the body’s natural vascular system.

Progress is being made though; recently a big breakthrough came when scientists successfully implanted functional 3D printed blood vessels into rhesus monkeys. This week, another step was taken when nanoengineers at the University of California, San Diego announced that they have 3D printed blood vessels that branch out into smaller vessels, creating a network that can safely and effectively integrate with the body’s vascular systems to circulate blood.

The research team was led by Dr. Shaochen Chen, head of the Nanobiomaterials, Bioprinting, and Tissue Engineering Lab at UC San Diego. Dr. Chen and his lab have been responsible for several tissue engineering and 3D printing breakthroughs, including the development of advanced bioprinted liver tissue and nanoscale 3D printed robotic fish designed to remove toxins in the body.

“Almost all tissues and organs need blood vessels to survive and work properly. This is a big bottleneck in making organ transplants, which are in high demand but in short supply,” said Dr. Chen. “3D bioprinting organs can help bridge this gap, and our lab has taken a big step toward that goal.”

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Dr. Shaochen Chen 3D prints a blood vessel network in his lab. [Image: Erik Jepsen/UC San Diego Publications]

Dr. Chen and his team have developed a novel bioprinting process that begins by creating a 3D model of a structure, such as a liver or vascular network, on a computer, which then transfers 2D snapshots of the model to millions of microscopic mirrors. The mirrors are digitally controlled to project the snapshots in the form of UV light onto a solution of light-sensitive polymers and live cells, which solidifies when exposed to the light. This process repeats, layer by layer, until a scaffold containing live cells, which will then grow into tissue, has been printed. The process, called microscale continuous optical printing (µCOP), takes only a few seconds and has been successfully used in the creation of the liver tissue and nanobots described above, as well as in the printing of the blood vessel network.

“We can directly print detailed microvasculature structures in extremely high resolution. Other 3D printing technologies produce the equivalent of ‘pixelated’ structures in comparison and usually require sacrificial materials and additional steps to create the vessels,” said Wei Zhu, a postdoctoral scholar in Dr. Chen’s lab and a lead researcher on the project.

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[Image: Chen Laboratory]

Dr. Chen and his team used medical imaging to create a 3D model of a blood vessel network, which they printed using endothelial cells, the cells that form the inner lining of blood vessels. The printed vessels grew into tissue after in vitro cultivation for only one day, and were then implanted into mice through wounds in the skin. Two weeks later, the researchers examined the mice and discovered that the implanted vessels had successfully merged with their existing blood vessel network and were circulating blood.

The 3D printed blood vessel structure measures 4 x 5 mm and is 6 micrometers thick, which is about the thickness of 12 strands of hair. The vessels still need further work; although they can circulate blood, they aren’t yet capable of transporting nutrients or waste.

“We still have a lot of work to do to improve these materials,” said Dr. Chen. “This is a promising step toward the future of tissue regeneration and repair.”

Dr. Chen and his lab plan to pursue additional research into the creation of patient-specific tissues from human induced pluripotent stem cells taken from the skin of the patient, preventing the risk of rejection. Eventually, they want to take their research into clinical trials, although Dr. Chen notes that it will be several years before they get to that point.

The blood vessel study has been published in a paper entitled “Direct 3D bioprinting of prevascularized tissue constructs with complex microarchitecture,” which you can access here. Study authors include Wei Zhu, Xin Qu, and Jie Zhu, Xuanyi Ma, Sherrina Patel, Justin Liu, Pengrui Wang, Cheuk Sun Edwin Lai, Yang Xu, Kang Zhang and Shaochen Chen of UC San Diego; and Maling Gou of Sichuan University. Discuss in the 3D Printed Blood Vessels forum at 3DPB.com.

 

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