Posted on by Dr. Francis Collins
There’s considerable excitement that 3D printing technology might one day allow scientists to produce fully functional replacement organs from one’s own cells. While there’s still a lot to learn, this video shows just some of the amazing progress that’s now being made.
The video comes from a bioengineering team at Rice University, Houston, that has learned to bioprint the small air sacs in the lungs. When hooked up to a machine that pulsed air in and out of the air sacs, the rhythmic movement helped to mix red blood cells traveling through an associated blood vessel network. Those red cells also took up oxygen in much the way that blood vessels do when surrounding the hundreds of millions of air sacs in our lungs.
As mentioned in the video, one of the biggest technical hurdles in growing fully functional replacement tissues and organs is to find a way to feed the growing tissues with a blood supply and to remove waste products. In this study recently published in Science , the NIH-supported team cleared this hurdle by creating an open-source bioprinting technology they call SLATE, which is short for “stereo-lithography apparatus for tissue engineering.”
The SLATE system “grows” soft hydrogel scaffolds one layer at a time. Each layer is printed using a liquid pre-hydrogel solution that solidifies when exposed to blue light. By also projecting light into the hydrogel as a pixelated 3D shape, it’s possible to print complex 3D structures within minutes.
When the researchers first started, their printouts lacked the high resolution, submillimeter-scale channels needed to generate intricate vascular networks. In other manufacturing arenas, light-absorbing chemicals have helped control the conversion from liquid to solid in a very fine polymer layer. But these industrial light-absorbing chemicals are highly toxic and therefore unsuitable for scaffolds that grow living tissues and organs.
The researchers, including Bagrat Grigoryan, Jordan Miller, and Kelly Stevens, wondered whether they could swap out those noxious ingredients with synthetic and natural food dyes widely used in the food industry. These dyes include curcumin, anthocyanin, and tartrazine (yellow dye #5). Their studies showed that those fully biocompatible dyes worked as effective light absorbers, allowing the scientists to recreate the complex architectures of human vasculature. Importantly, the living cells survived within the soft scaffold!
These models are already yielding intriguing new insights into the vascular structures found within our organs and how those architectures may influence function in ways that hadn’t been well understood. In the near term, tissues and organs grown on such scaffolds might also find use as sophisticated, 3D tissue “chips,” with potential for use in studies to predict whether drugs will be safe in humans.
In the long term, this technology may allow production of replacement organs from those needing them. More than 100,000 men, women, and children are on the national transplant waiting list in the United States alone and 20 people die each day waiting for a transplant . Ultimately, with the aid of bioprinting advances like this one, perhaps one day we’ll have a ready supply of perfectly matched and fully functional organs.
 Multivascular networks and functional intravascular topologies within biocompatible hydrogels. Grigoryan B, Paulsen SJ, Corbett DC, Sazer DW, Fortin CL, Zaita AJ, Greenfield PT, Calafat NJ, Gounley JP, Ta AH, Johansson F, Randles A, Rosenkrantz JE, Louis-Rosenberg JD, Galie PA, Stevens KR, Miller JS. Science. 2019 May 3;364(6439):458-464.
 Organ Donor Statistics, Health Resources & Services Administration, October 2018.
Tissue Engineering and Regenerative Medicine (National Institute of Biomedical Imaging and Bioengineering/NIH)
Tissue Chip for Drug Screening (National Center for Advancing Translational Sciences/NIH)
Miller Lab (Rice University, Houston)
NIH Support: National Heart, Lung, and Blood Institute; National Institute of Biomedical Imaging and Bioengineering; National Institute of General Medical Sciences; Common Fund
Posted on by Dr. Francis Collins
For people whose spinal cords are injured in traffic accidents, sports mishaps, or other traumatic events, cell-based treatments have emerged as a potential avenue for encouraging healing. Now, taking advantage of advances in 3D printing technology, researchers have created customized implants that may boost the power of cell-based therapies for repairing injured spinal cords.
Made of soft hydrogels that mimic spinal cord tissue, the implant pictured here measures just 2 millimeters across and is about as thick as a penny. It was specially designed to encourage healing in rats with spinal cord injuries. The tiny, open channels that surround the solid “H”-shaped core are designed to guide the growth of new neural extensions, keeping them aligned properly with the spinal cord.
When left on their own, neural cells have a tendency to grow haphazardly. But the 3D-printed implant is engineered to act as a scaffold, keeping new cells directed toward the goal of patching up the injured part of the spinal cord.
For the new work, an NIH-funded research team, led by Jacob Koffler, Wei Zhu, Shaochen Chen, and Mark Tuszynski of the University of California, San Diego (UCSD), used an innovative 3D printing technology called microscale continuous projection printing. This technology relies on a computer projection system and precisely controlled mirrors, which direct light into a solution containing photo-sensitive polymers and cells to produce the final product. Using this approach, the researchers fabricated finely detailed, rodent-sized implants in less than 2 seconds. That’s about 1,000 times faster than a traditional 3D printer!
In a study published recently in Nature Medicine, the researchers placed their custom-made implants, loaded with rat embryonic neural stem cells, into the injured spinal cords of 11 rats. Other rats with similar injuries received empty implants or stem cells without the implant. Within 5 months, rats with the cell-loaded implants had new neural cells bridging the injured area, along with spontaneous regrowth of blood vessels to feed the new neural tissue. Most importantly, they had regained use of their hind limbs. Animals receiving empty implants or cell-based therapy without an implant didn’t show that kind of recovery.
The new findings offer proof-of-principle that 3D printing technology can be used to create implants tailored to the precise shape and size of an injury. In fact, the researchers have already scaled up the process to produce 4-centimeter-sized implants to match several different, complex spinal cord injuries in humans. These implants were printed in a mere 10 minutes.
The UCSD team continues to work on further improvements, including the addition of growth factors or other ingredients that may further encourage neuron growth and functional recovery. If all goes well, the team hopes to launch human clinical trials of their cell-based treatments for spinal cord injury within a few years. And that should provide hope for the hundreds of thousands of people around the world who suffer serious spinal cord injuries each year.
 Biomimetic 3D-printed scaffolds for spinal cord injury repair. Koffler J, Zhu W, Qu X, Platoshyn O, Dulin JN, Brock J, Graham L, Lu P, Sakamoto J, Marsala M, Chen S, Tuszynski MH. Nat Med. 2019 Feb;25(2):263-269.
Spinal Cord Injury Information Page (National Institute of Neurological Disorders and Stroke/NIH)
Stem Cell Information (NIH)
Koffler Lab (University of California, San Diego)
Shaochen Chen (UCSD)
Tuszynski Lab (UCSD)
NIH Support: National Institute of Biomedical Imaging and Bioengineering; National Institute of Child Health and Human Development
Posted on by Dr. Francis Collins
Researchers have learned in recent years how to grow miniature human hearts in a dish. These “organoids” beat like the real thing and have allowed researchers to model many key aspects of how the heart works. What’s been really tough to model in a dish is how stresses on hearts that are genetically abnormal, such as in inherited familial cardiomyopathies, put people at greater risk for cardiac problems.
Enter the lab-grown human cardiac tissue pictured above. This healthy tissue comprised of the heart’s muscle cells, or cardiomyocytes (green, nuclei in red), was derived from induced pluripotent stem (iPS) cells. These cells are derived from adult skin or blood cells that are genetically reprogrammed to have the potential to develop into many different types of cells, including cardiomyocytes.