Boeingโ€™s Technology in Space program gives a boost to start-ups working on biomedical innovations by funding their experiments on the International Space Station.

In July 2016, Nicole Wagner was sitting at her desk at the MassChallenge co-working space in South Boston. Wagner, president and CEO of Farmington, Conn.-based LambdaVision Inc., was carpooling three times a week with her chief science officer, Jordan Greco, to participate in the startup accelerator program. The commute was 90 minutes each way, including dropping off Wagnerโ€™s toddler at her momโ€™s for childcare. As a scientist, entrepreneur, wife and mom, Wagner said, her days were typically beyond packed.

โ€œThe MassChallenge team came around and said Boeing and the ISS National Lab are down the hall for a presentation,โ€ Wagner said. Her initial thought was that the event must be about moon missions and Mars. She couldnโ€™t imagine how it would be helpful for LambdaVisionโ€™s workโ€”developing a protein-based artificial retina to restore functional sight to the millions of patients blinded by retinal degenerative diseases. But this summer day was uncharacteristically and fortuitously under-scheduled. โ€œWhy not,โ€ she said. โ€œLetโ€™s check it out.โ€

At the presentation, Wagner learned about a program called Technology in Spaceโ€”a partnership between Boeing, the International Space Station U.S. National Laboratory and MassChallenge. She realized that perhaps microgravity could be the missing puzzle piece in the manufacturing process for their protein-based thin films. LambdaVisionโ€™s layer-by-layer process is influenced by gravity, which means sedimentation and gradients of solutions interfere with the quality of the multilayered implants. Wagner and her colleagues had talked to many engineers and contract manufacturing organizations about ways to make the artificial retina on Earth, and each method had challengesโ€”which often came back to gravity. If manufacturing in a microgravity environment created a higher quality prototype, it would optimize performance for future preclinical and clinical trials.

LambdaVision entered the Technology in Space competition and within four months of Boeingโ€™s presentation, the start-up was awarded the Technology in Space Prize, which provided seed funding for research on the space station. Wagner and her team knew this could be a game-changer.

Using microgravity in space to better life on Earth

Boeingโ€™s Technology in Space program was founded in 2014 by Scott Copeland, ISS Research Integration Director, and Kevin Foley, ISS and Low-Earth Orbit Commercialization Programs Director, to better educate those in the start-up community on the opportunities for research onboard the orbiting laboratory. Since then, the program has allocated more than $4.5 million in funding to 18 start-up companies. The awards allow startups to leverage the microgravity environment onboard the ISS National Lab to drive product development and innovation.

โ€œLow Earth Orbit gives you a unique environment,โ€ said Copeland. โ€œWhether itโ€™s engineering or biology, everything works differently in microgravity. Cells react a little bit differently, viruses become more virulent.โ€ Taking advantage of those changes, Copeland said, can help biomedical researchers understand how to potentially come up with a cure or a pharmaceutical that will benefit us on Earth.

Of course, astronauts have been running experiments on the ISS since its early days. But for years, while the station was under construction, research was limited to about 20 hours a week. Today, Copeland said, some astronauts are working on experiments full-time. โ€œWeโ€™re getting about 75 hours of crew science done per week.โ€

Each ISS crew performs a few hundred experiments during their months-long stays on orbit. Some take place over a short time while others carry on for a number of years gathering data, such as physiological studies on crewmember reactions to microgravity. Because the amount of research is so much higher than aboard any spacecraft before, there is much more opportunity for scientists to take advantage of the space environment in fields that have not had that chance before. Even high school students can fly experiments aboard the station in a similar program called Genes in Space.

When the Boeing duo began spreading the word about Technology in Space in 2014 through MassChallenge, โ€œPeople didnโ€™t know what we were talking about,โ€ Foley said. โ€œFast forward to 2022, and thereโ€™s enough information out there about the value of research in space that thereโ€™s now a keen interest in it.โ€ Every year, he and Copeland present an overview of the program to 125 start-ups in Boston, followed by a fast-pitch sessionโ€”that Copeland compares to speed datingโ€”in which the companies share their ideas.

โ€œWe evaluate those and narrow it down to 20 to 30 and then look at their technology to see whether a research and development campaign on the ISS might be beneficial to their work,โ€ Foley said. โ€œWe try to select as many as we can. I wish we could take all of them so more people could have the experience of conducting research in space.โ€

Technology in Space prizes have funded a wide range of these experiments. For example:

  • CamMed tested a bandage-like patch pump for subcutaneous delivery of medications;
  • miniPCR developed a platform that enables DNA analysis at a fraction of the cost, and set up a machine that allows crew members to make copies of specific segments of DNA on the ISS;
  • Droplette tested a device that allows for large-molecule drugs to be delivered through the skin;
  • Angiex tested the novel cancer therapy that targets both tumor cells and the endothelial cells of tumor blood vessels; and
  • Biorasis worked to improve accuracy of medically implantable glucose biosensors for diabetes management.

โ€œYour experiments are on that rocket.โ€

After LambdaVision was selected for the Technology in Space program, Boeing and the ISS National Lab helped the team join forces with implementation partner Space Tango to miniaturize the layering device for a smaller laboratory setting and to design the ISS experiments.

โ€œAs a scientist whoโ€™s traditionally done bench work on the ground, it was a very different thought process for me,โ€ said Wagner, who serves as the chair of the Applied Research and Development Subcommittee, part of the ISS National Labโ€™s User Advisory Committee. โ€œHow do we take this open beaker system and prepare it for the ISS?โ€

LambdaVisionโ€™s first experiment was part of the payload that launched to the ISS in December 2018. Wagner and Grecco watched the launch from Kennedy Space Center after sitting in on a briefing which covered all the experiments on board. โ€œThey told us that weโ€™ll want to take pictures, but that we could always find pictures online,โ€ Wagner said. โ€œInstead, we should just take it all in.โ€ She said watching a launch was a bucket list item that she didnโ€™t even know was on her bucket list. โ€œIt was so cool. Youโ€™re watching a rocket launch, and your experiments are on that rocket.โ€

The research on that first launch resulted in the proof of concept for creating multilayered thin films using a Low-Earth Orbit platform. โ€œThe big milestone was that this was one of the first times anything has been manufactured in space that could have clinical application,โ€ Wagner said.

LambdaVisionโ€™s work was recognized in 2019 at the ISS Research and Development Conference with the ISS Research and Development Award in Medicine in Biology. The company then received a Small Business Innovation Research Phase I grant from NASA in 2019 to perform a series of terrestrial-based parameterization experiments for follow-on spaceflight optimization, and a Small Business Innovation Research Phase II grant, as well as a NASA Research Announcement with Space Tango to support additional flights to the ISS. LambdaVision has now sent four experiments to space.

Wagner said her young children have been very enthusiastic about LambdaVisionโ€™s research in space. Her daughter built a Lego rocket ship in school and wrapped it in foil so it could fly near the sun for deep exploration. โ€œEvery time she sees a plane in the sky, she asks, โ€˜Mom, is that your rocket?โ€™โ€ Wagner said. She looks forward to the day when she can take her kids to a launch. That opportunity may come as soon as April, which will mark LambdaVisionโ€™s fifth mission to space.

Bone super glue travel to space

RevBio is a Lowell, Mass.-based medical device company that makes a patented bone adhesive called Tetranite, which fixes fractures and accelerates bone repairโ€”especially in patients suffering from osteoporosis. After learning that even a short stay in microgravity can cause loss of bone mass, the company entered the Technology in Space competition and was awarded the prize in 2015.

RevBioโ€™s first ISS mission was an in vitro experiment focused on the response of osteoblasts (a bone subtype) to Tetranite. RevBio is now preparing for its second mission in October, an in vivo experiment using Tetranite to treat 40 mice with artificially created bone defects while concurrently experimenting on 40 control mice on Earth to study the differences in microgravity. The experiment will examine the biomaterialโ€™s osteoconductivity when used in a microgravity environment where bone density and the ability to regenerate new bone tissue is significantly compromised.

The general theory, said principal investigator and University of Pittsburgh School of Dental Medicine associate professor Giuseppe Intini, who studies the biology of bone, is that microgravity impairs bone tissue regeneration by inhibiting differentiation of skeletal stem cells, and that Tetranite can reverse this inhibition and promote bone regeneration.

โ€œWeโ€™re going to investigate how Tetraniteโ€”a bone super glue thatโ€™s also injectable as a bone fillerโ€”behaves in space,โ€ said Intini. โ€œThe hypothesis is that the Tetranite will be able to stimulate the skeletal stem cells and promote bone formation and regeneration. Many people suffer from osteoporosis, and this could be extremely useful to treat those fractures on Earth.โ€

The company is initially developing this technology for use in the dental market and recently initiated two clinical studies for the use of Tetranite to immediately stabilize dental implants placed in sites that lack sufficient primary stability. The company is also working to develop adhesive applications for the broader orthopedics market.

Transforming cancer treatment with microgravity

MicroQuin, a Cambridge, MA.-based start-up and part of the LabCentral incubator, are creating revolutionary therapeutics that will transform the standard of care for cancer. It is developing therapies that target cancerous cells to induce rapid cell death with minimal to no toxicity and immunogenicity. โ€œWe want to develop better therapeutics to help patients recover quicker and also reduce the toxicity associated with cancer treatment,โ€ said MicroQuin President and CEO Scott Robinson.

MicroQuin sent its first Boeing and ISS National Lab-sponsored experiment to ISS in 2018, studying therapeutics to modulate the protein TMBIM6โ€”which regulates stress and is essential in cancer cell survival and spread. MicroQuin has found a way of turning off TMBIM6 in cancer cells only; if it canโ€™t regulate stress in the cancer cells, Robinson said, the cancer essentially stresses itself to death.

โ€œThat first mission was an amazing success,โ€ said Robinson, whose expertise is in cell deathโ€”which he noted cancer is good at avoiding. He explained that the TMBIM6 protein changes its structure in response to the environment, but that structure has proven difficult to predictโ€”even for artificial intelligence. The missing link, it turned out, was microgravity found in orbit.

Robinson said crystals in microgravity can grow larger over a longer period of time, so they can more easily study hard-to-crystallize proteins like TMBIM6. โ€œYou can get these large, beautiful crystals growing,โ€ said Robinson. โ€œThat changes everything. The work on the space station is totally key for us.โ€

MicroQuin, which Robinson said is the only company in the world to know anything about the target proteinโ€™s structure, has made therapeutics that inhibit the proteinโ€™s ability to regulate the harsh cancer cell environment. Those therapeutics have in several cases killed the cancer outright, with an impressive 70 to 95 percent cancer cell death in animal models. โ€œFor certain cancers these drugs are fantastic and could be a monotherapy,โ€ Robinson said. โ€œFor other cancers they would significantly improve standard of care.โ€

In February, MicroQuin sent its second mission to the ISS to examine the effects of a drug on breast and prostate cancer cells in space. Results could provide new insight into how TMBIM6 is affected by the drug and help advance development of other drugs that target cancerous cells.

On Earth, cancer cells form a monolayer in a test tube. โ€œBut when you get cancer, itโ€™s three-dimensionalโ€”a tumor, more like a ball,โ€ Robinson said. โ€œSo the cell signaling is very different from a single layer. In a ball, for example, cancer cells have varied access to oxygen and nutrients. In microgravity, we can look at how this impacts signaling and can get more natural, three-dimensional modelsโ€”similar to what they are in the body.โ€

Robinson joked that he offered himself to conduct the experiments on the ISS, but, he said, โ€œThere seemed to be a little more training than going to the gym.โ€ Despite that disappointment, Robinson said the entire process has been โ€œoutstandingโ€ and a dream come true.

โ€œCancer is a horrible disease, and itโ€™s very natural; it affects about one in three people in their lifetime โ€” thatโ€™s astronomical,โ€ Robinson said. โ€œWeโ€™ve had the opportunity to go to space and do something thatโ€™s not just cool but can really change technology and give a massive offering to the world. This really wouldnโ€™t have been possible if it werenโ€™t for Boeing and the ISS National Lab. We wouldnโ€™t have these drugs for TMBIM6.โ€