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Progress Toward 3D Printed Human Organs

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 [1], 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 [2]. 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.

References:

[1] 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.

[2] Organ Donor Statistics, Health Resources & Services Administration, October 2018.

Links:

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


Seven More Awesome Technologies Made Possible by Your Tax Dollars

Posted on by Dr. Francis Collins

We live in a world energized by technological advances, from that new app on your smartphone to drones and self-driving cars. As you can see from this video, NIH-supported researchers are also major contributors, developing a wide range of amazing biomedical technologies that offer tremendous potential to improve our health.

Produced by the NIH’s National Institute of Biomedical Imaging and Bioengineering (NIBIB), this video starts by showcasing some cool fluorescent markers that are custom-designed to light up specific cells in the body. This technology is already helping surgeons see and remove tumor cells with greater precision in people with head and neck cancer [1]. Further down the road, it might also be used to light up nerves, which can be very difficult to see—and spare—during operations for cancer and other conditions.

Other great things to come include:

  • A wearable tattoo that detects alcohol levels in perspiration and wirelessly transmits the information to a smartphone.
  • Flexible coils that produce high quality images during magnetic resonance imaging (MRI) [2-3]. In the future, these individualized, screen-printed coils may improve the comfort and decrease the scan times of people undergoing MRI, especially infants and small children.
  • A time-release capsule filled with a star-shaped polymer containing the anti-malarial drug ivermectin. The capsule slowly dissolves in the stomach over two weeks, with the goal of reducing the need for daily doses of ivermectin to prevent malaria infections in at-risk people [4].
  • A new radiotracer to detect prostate cancer that has spread to other parts of the body. Early clinical trial results show the radiotracer, made up of carrier molecules bonded tightly to a radioactive atom, appears to be safe and effective [5].
  • A new supercooling technique that promises to extend the time that organs donated for transplantation can remain viable outside the body [6-7]. For example, current technology can preserve donated livers outside the body for just 24 hours. In animal studies, this new technique quadruples that storage time to up to four days.
  • A wearable skin patch with dissolvable microneedles capable of effectively delivering an influenza vaccine. This painless technology, which has produced promising early results in humans, may offer a simple, affordable alternative to needle-and-syringe immunization [8].

If you like what you see here, be sure to check out this previous NIH video that shows six more awesome biomedical technologies that your tax dollars are helping to create. So, let me extend a big thanks to you from those of us at NIH—and from all Americans who care about the future of their health—for your strong, continued support!

References:

[1] Image-guided surgery in cancer: A strategy to reduce incidence of positive surgical margins. Wiley Interdiscip Rev Syst Biol Med. 2018 Feb 23.

[2] Screen-printed flexible MRI receive coils. Corea JR, Flynn AM, Lechêne B, Scott G, Reed GD, Shin PJ, Lustig M, Arias AC. Nat Commun. 2016 Mar 10;7:10839.

[3] Printed Receive Coils with High Acoustic Transparency for Magnetic Resonance Guided Focused Ultrasound. Corea J, Ye P, Seo D, Butts-Pauly K, Arias AC, Lustig M. Sci Rep. 2018 Feb 21;8(1):3392.

[4] Oral, ultra-long-lasting drug delivery: Application toward malaria elimination goals. Bellinger AM, Jafari M1, Grant TM, Zhang S, Slater HC, Wenger EA, Mo S, Lee YL, Mazdiyasni H, Kogan L, Barman R, Cleveland C, Booth L, Bensel T, Minahan D, Hurowitz HM, Tai T, Daily J, Nikolic B, Wood L, Eckhoff PA, Langer R, Traverso G. Sci Transl Med. 2016 Nov 16;8(365):365ra157.

[5] Clinical Translation of a Dual Integrin avb3– and Gastrin-Releasing Peptide Receptor–Targeting PET Radiotracer, 68Ga-BBN-RGD. Zhang J, Niu G, Lang L, Li F, Fan X, Yan X, Yao S, Yan W, Huo L, Chen L, Li Z, Zhu Z, Chen X. J Nucl Med. 2017 Feb;58(2):228-234.

[6] Supercooling enables long-term transplantation survival following 4 days of liver preservation. Berendsen TA, Bruinsma BG, Puts CF, Saeidi N, Usta OB, Uygun BE, Izamis ML, Toner M, Yarmush ML, Uygun K. Nat Med. 2014 Jul;20(7):790-793.

[7] The promise of organ and tissue preservation to transform medicine. Giwa S, Lewis JK, Alvarez L, Langer R, Roth AE, et a. Nat Biotechnol. 2017 Jun 7;35(6):530-542.

[8] The safety, immunogenicity, and acceptability of inactivated influenza vaccine delivered by microneedle patch (TIV-MNP 2015): a randomised, partly blinded, placebo-controlled, phase 1 trial. Rouphael NG, Paine M, Mosley R, Henry S, McAllister DV, Kalluri H, Pewin W, Frew PM, Yu T, Thornburg NJ, Kabbani S, Lai L, Vassilieva EV, Skountzou I, Compans RW, Mulligan MJ, Prausnitz MR; TIV-MNP 2015 Study Group.

Links:

National Institute of Biomedical Imaging and Bioengineering (NIH)

Center for Wearable Sensors (University of California, San Diego)

Hyperpolarized MRI Technology Resource Center (University of California, San Francisco)

Center for Engineering in Medicine (Massachusetts General Hospital, Boston)

Center for Drug Design, Development and Delivery (Georgia Tech University, Atlanta)

NIH Support: National Institute of Biomedical Imaging and Bioengineering; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Allergy and Infectious Diseases