Indianapolis VA Medical Center and NASA To Explore 3D Bioprinting for Healthcare

Exposure to space radiation, gravity fields, contaminated atmospheres, are all part of the hostile environment astronauts encounter beyond Earth’s orbit. As they transition from one gravity field to another, the fluids in their body can shift upwards, which could lead to pressure on the eyes causing vision problems, among other pretty scary diseases that the National Aeronautics and Space Administration (NASA) has been working to solve for decades as they prepare to send humans on three-year missions to Mars.

NASA wants to make sure that tissue replacement beyond the repairing ability of the organism can be done in space. However, such a scheme would also mean that space agencies will have to plan way ahead of departure on how to leverage innovative technologies, like 3D printing, to aid astronauts on their journey, while directly contributing to their respective development efforts. That is what several United States government agencies are doing, including the Veterans Administration and NASA. More particularly, scientists at the Indianapolis Richard L. Roudebush Veterans Affairs (VA) Medical Center and NASA investigators are now jointly exploring new approaches to 3D bioprinting. The two teams are collaborating in the conversion of human and animal eye fundus images into virtual renderings of the retinal vascular networks for bioprinting. Exploring this field, will not only serve NASA’s interest in space, but also the VA’s concerns here on Earth since tissue replacement is often needed to treat combat, accident or disease-induced damage to veterans.

One of the most serious limitations for the success of tissue engineering, and in particular of the bioprinting approaches to generate artificial tissues, is the difficulty to perfuse the constructs with oxygenated fluids and nutrients. To tackle this issue, Patricia Parsons-Wingerter, senior scientist at NASA’s Space Biosciences Research Branch, and her NASA-wide team joined forces with Nicanor I. Moldovan, founding director of the 3D Bioprinting Core (3DBPC) laboratory at the Richard L. Roudebush VA Medical Center. 

Patricia Parsons-Wingerter (Credit: NASA)

Such combined efforts could bring unprecedented success for the bioprinting of vascular networks. In this instance, the NASA team will use their innovative Vessel Generation Analysis (VESGEN) 2D software application for the design of anatomically realistic vascular patterns for bioprinting, while the Indianapolis-based team will provide their know-how on bioprinting vascular models.

In fact, Parsons-Wingerter and her colleagues developed VESGEN 2D, an image analysis program that performs branching quantification of vascular networks, in order to assist in the early detection of changes in vascular patterns of the eye, which may indicate microgravity-induced retinopathy, also the major blinding disease of working-aged adults. However, vascular-dependent diseases include cancer, diabetes, coronary vessel disease, and major astronaut health challenges in the space microgravity and radiation environments, especially for long-duration missions. In this sense, VESGEN 2D maps and quantifies vascular remodeling for a wide variety of quasi-2D vascularized biomedical tissue applications

Parsons-Wingerter’s concern with eyesight problems related to space travel has been historically well-founded. According to one study sponsored by NASA several years ago, space flights that last six months or longer can cause changes in astronauts’ eyes and vision. At the time, this discovery had a major impact on plans for a manned flight to Mars, making this a top priority for NASA’s Space Medicine research team. During the study, seven astronauts that were examined had eye structure and vision abnormalities, most commonly the flattening of the back of the eyeball, changes in the retina (the light-sensitive area at the back of the eye) as well as the optic nerve. Knowing now that vision can be severely compromised in space now demands a lot of attention from researchers, especially, since astronauts, like airline pilots, must have 20/20 vision to carry out most of their work in orbit.

According to Parsons-Wingerter, VESGEN is in fact, currently being used to help understand and ameliorate vision impairments in astronauts and terrestrial adults diagnosed with diabetic retinopathy. And it’s no surprise that VESGEN 2D will be utilized to aid in the design of anatomically realistic vascular patterns for bioprinting since this image analysis program offers insightful read-outs (or biomarkers) of dominant molecular signaling targeted by drug and therapeutic development. 

Composite images and journal cover illustrations of vascular patterning collaborations with other scientists for VESGEN research (Credit: NASA)

Meanwhile, Moldovan’s 3DBPC laboratory (also known to many as the “Core”) primarily serves the VA investigators’ needs, helping with workflow design and implementation from project conception through funding and execution. More specifically, the Core provides assistance with hydrogels preparation, bioinks characterization, cell cultivation, samples mixing, 3D model printing, cell-containing constructs bioprinting, incubation, perfusion, and characterization (by fluorescence microscopy, micro, and macro photography), up to data analysis and preparation for publication. Current activities in the Core include the generation of bone, cartilage, retinal, neural, and other 3D models.

Nicanor Moldovan (Credit: 3D Tissue Bioprinting Core at VAMC)

Funded and administered by the Indiana Institute of Medical Research (IIMR) and supporting the overall research mission of the Veterans Affairs Medical Center in Indianapolis, the Core features the bioprinter 3DDiscovery, which was purchased from Swiss company regenHU through a VA Shared Equipment Evaluation Program (ShEEP) grant. 

Another example of the commitment of government agencies to work together to develop healthcare solutions for the future, the Richard L. Roudebush VA Medical Center has also recently joined NASA’s centennial Vascular Tissue Challenge, a project that rallies scientists worldwide to produce viable thick-tissue assays that can be used to advance research on human physiology. NASA began the Vascular Tissue Challenge in May 2019, in collaboration with the Methuselah Foundation and thanks to the support from the New Organ Alliance (NOA), a non-profit organization aiming to catalyze the tissue engineering field. Roudebush VA Medical Center’s Moldovan is also participating in this venture as chair of the NOA’s In Vitro Tissue Models Sub-Committee.

Considering that one of the main projects in the Core is the bioprinting of vascular models, this new joint effort with Parsons-Wingerter is considered by them as a natural step to move forward the research for both teams. In fact, the same approach with VESGEN 2D can be used for the realistic representation, and the adaptation to the printable format of vascular networks of other organs, such as rat mesentery or mouse colon, to be incorporated as region-specific cellular compositions in actual bioprinted tissue constructs. The teams claim that these constructs will be useful both as in vitro models for mechanistic studies and drug discovery and for the eventual replacement of damaged tissues or organs. After all, that is exactly what NASA and the VA are aiming for, both here and in space.

Considering that the US space agency has recently asserted its goal of sending astronauts to Mars once again, researchers, like Parsons-Wingerter and Moldovan, are crucial to the future mission’s, success. This is especially relevant since such Mars missions would last from seven months to two or more years. As they continue to solve many of the health-related issues attached to long-duration space expeditions, we will surely find out more about their work as they combine creative talents to develop more bioprinting innovation. 

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CELLINK and Uppsala University Send Stem Cells to Space

CELLINK and Uppsala University send stem cells to space

To study the influence of microgravity and hypergravity on living systems, bioprinting pioneer CELLINK, in collaboration with a team of scientists at Uppsala University, has sent 3D bioprinted boundary cap neural crest stem cells to space. The partnership is aiming to accelerate the development of a 3D neural stem cell system to provide insight on how gravity alterations influence cellular properties. According to the Department of Neuroscience at Uppsala University’s Faculty of Medicine, these so-called boundary cap neural crest stem cells are a transient cell population residing at the junction between dorsal roots and spinal cord during embryonic development. In 2014, researchers at the university conducted studies that showed how growth, survival and function of insulin-producing cells in the pancreas are promoted if the cells are cultured or transplanted together with boundary cap neural crest stem cells, providing novel opportunities to treat patients with type one diabetes.

The stem cells prior to launch

CELLINK’s BIO X bioprinter and bioinks were used to bioprint boundary cap neural crest stem cells that were successfully launched to space on June 24 on Maser14 by the Swedish National Space Agency. The cells were supplied by Uppsala University and printed using CELLINK Bioink and CELLINK GelMA.

CELLINK BIO X Bioprinter used by Uppsala University

“Our mission to help improve the physical conditions for astronauts with Uppsala University is a huge milestone for CELLINK. The strenuous conditions astronauts face while in space has been a widely talked about subject and this week we took the first step towards helping solve this problem. Understanding the effects of microgravity is a crucial element to this equation.  We have worked extremely hard on developing technology that will help change the world and are very much looking forward to sharing the first set of results as soon as they become available,” suggestedItedale Redwan, Chief Science Officer at CELLINK, to 3DPrint.com.

Space exploration challenges the limits of human physiology, and advancing capabilities in spaceflight require innovative solutions from frontline scientists across fields of physics, biology, and medicine. This is why CELLINK, the world’s first bioink company, continually seeks new partnerships and collaborations to provide researchers with emerging capabilities and innovations in the field. The startup has already managed to print human skin and is also working on producing liver tissues, as well as the beta cells that produce the insulin we need to survive.

This is not the first collaboration between CELLINK and Uppsala University, the company has worked with Associate Professor Joey Lau Börjesson to use 3D bioprinting to create a favourable microenvironment for transplanted insulin-producing cells. At the time Börjesson used 3D bioprinter INKREDIBLE to bioprint human pancreatic islets with CELLINK’s bioink PAN X, with extracellular matrix proteins derived from human pancreas and used to mimic the physiological microenvironment for the pancreatic islets of Langerhans (which have a dense network of blood vessels facilitating delivery of the produced hormones which regulate the blood glucose levels). The group mixed human islets with the PAN X bioink and bioprinted grid-shaped constructs, showing that the function in human islets is improved when bioprinted with the bioink; moreover, the human islets demonstrated intact morphology after bioprinting.

There are other projects to bioprint in space on the way, like nScrypt‘s 3D BioFabrication Facility (BFF) set to launch sometime this year to the International Space Station (ISS) aboard a cargo mission departing from the Air Force Station in Cape Canaveral, Florida. The first complete print, after the initial test prints, will be a cardiac patch for damaged hearts. While the Athlone Institute of Technology (AIT), under contract with the European Space Agency, will be creating a new, large-scale 3D printer capable of fabricating parts in a zero-gravity atmosphere. The innovative hardware will be used at the International Space Station (ISS) in connection with a European consortium to be known as ‘Project Imperial’ that includes Sonaca GroupBEEVERYCREATIVE, and OHB.

So, why is everyone so eager to send stem cells and bioprinters to space? For one, microgravity has an effect on astronauts health and stem cell research could shed light on what the effects of long missions in space could cause to the human body. In 2013, mouse embryonic stem cells were transported to the ISS to investigate the impact of long-term space flight on human health. This, like many other projects, arose after previous studies found astronauts and animals returning from space have damage to their immune or reproductive systems, which might be caused by microgravity, radiation or even stress. It seems that sending stem cells to space could not only help mitigate some of these factors but also aid in the development of new drugs to combat them.

Image Credit: CELLINK

Allevi and Made In Space Partner Up for New Initiative: 3D Bioprinting in Outer Space

3D bioprinting company Allevi, formerly known as BioBots, is on a mission to make it easier for scientists and researchers to design and engineer 3D tissues. The company, which was founded four years ago, develops 3D bioprinters, software, and bioinks for the purposes of solving the most difficult biomedical problems that plague our world, such as disease and eliminating the organ waiting list.

But now, Allevi is preparing to take its 3D bioprinting work out of this world with a new initiative.

Ever since the space race began in the late 1950s and led to the first man on the moon, humanity has been working hard to conquer the vastness of outer space. 3D printing has helped in this quest, from sending astronauts into space for research and testing and allowing them to fabricate items in zero gravity and microgravity to creating tools, medical supplies, and even habitats in space. Space exploration has also led to the creation of such practical tools on Earth as joysticks, GPS devices, and thermometers. This last brings us back to the medical sector, and Allevi’s goal of 3D bioprinting replacement organs for humans.

“While we continue to understand the capabilities and constraints of 3d biofabrication here on Earth, the ability to explore cellular function in space could afford us novel discoveries of organ form and function that have never before been studied,” Allevi wrote.

Astronauts can study things in a completely new way when they don’t have to worry about the constraints of gravity, and 3D printing can help increase their capabilities in these situations. This is one of the main focuses of California-based 3D printing and space technology firm Made In Space, which is responsible for introducing 3D printing to the International Space Station (ISS) four years ago. Having the ability to 3D print important parts and tools aboard the ISS helps the astronauts complete their tasks in space.

Now, Made In Space and Allevi are working together to develop the Allevi ZeroG – the first 3D bioprinter in space. The two companies jointly launched the initiative at the recent ISS Conference in San Francisco, and even found the first two users of the new 3D bioprinting platform in Astronauts Mark Vendei Hei and Randy Bresnik, who Allevi says are excited to be on board.

Allevi developed a compatible extruder, fittingly called the ZeroG bio-extruder, that is able to be outfitted onto Made In Space’s Additive Manufacturing Facility currently on board the ISS. This new bio-extruder will make it possible for scientists using the Allevi 3D bioprinting platform to run experiments in space, and back home on Earth, at the same time, in order to observe and study any biological differences that happen when 3D printing with gravity and without it.


“We are excited to continue to revolutionize how we study biology, not only on the ground but now in space,” Allevi wrote. “And perhaps one day, the Allevi ZeroG will aid astronauts in 3D bioprinting replacement organs for deep space travel. We’re excited to participate in this next generation space race.”

NASA and companies like Made In Space are already hard at work researching and creating tools to use and places to live in outer space. But if this Allevi initiative is successful, having the ability to create 3D bioprinted organs in space will bring us another step closer to living among the stars.

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[Images provided by Allevi]