Michigan has been pushing forward the field of biomedical engineering for over 50 years, with incredible technological contributions like ECMO, the silicon neural probe, and the spherocentric knee, to the world-class education of today’s top biomedical engineering minds.
Giant leaps forward in biomedical engineering are truly possibly when engineers and clinicians are given the environment to work in close proximity. From an engineered scaffold to aid in the early detection of breast cancer metastasis, to a controlled form of ultrasound to non-invasively destroy bad tissue in the body, to a determined mission to enable neural control of prosthetics, Michigan Biomedical Engineering is developing incredible solutions to the worlds most pressing biological and medical challenges.
Biomedical Engineering at the University of Michigan is poised to make incredible impact in the fields of engineering, biology and medicine in the years and decades ahead, from innovations in undergraduate and graduate education to groundbreaking research.
In a breakthrough that could one day lead to new treatments for lung diseases like asthma and lung cancer, researchers have successfully coaxed stem cells—the body’s master cells—to grow into three-dimensional lung tissue. This could be useful in future cell-based therapies that repair damaged lungs by cultivating new, healthy tissue.
University of Michigan researchers grew the tissue by injecting stem cells into a specially developed biodegradable scaffold, then implanting the device in mice, where the cells grew and matured into lung tissue. The team’s findings were published in the Nov. 1 issue of the journal eLife.
Respiratory diseases account for nearly 1 in 5 deaths worldwide, and lung cancer survival rates remain low despite numerous therapeutic advances during the past 30 years. Cell-based therapies could be a key to improving treatment, helping damaged lungs heal in much the same way as a bone marrow transplant can treat leukemia. But the complexity of lung tissue makes such treatments much more difficult to develop.
“Lung tissue needs to be able to form into specific structures like airways and bronchi, and they all need to be able to work together inside the lung. So we can’t just add in healthy adult cells,” said Lonnie Shea, the William and Valerie Hall Department Chair of Biomedical Engineering and a professor of biomedical engineering at U-M. “Instead, we’re looking at delivering the precursors to these cells, then giving them the cues they need to develop and mature on their own. This project was a step in that direction.”
While previous experiments had successfully grown lung cells, the cells were immature and disorganized. So Shea worked with a U-M medical school team led by Briana Dye, a graduate student in the U-M Department of Cell and Developmental Biology, on a new approach. They developed a three-dimensional, biodegradable scaffold that helped the lung cells mature and begin to develop into structures like those inside an actual lung.
Made of PLG, a spongy, biodegradable material, the scaffold was shaped like a small cylinder approximately five millimeters wide and two millimeters tall. The team injected stem cells into the scaffold, transplanted it into mice, then allowed the cells to mature for eight weeks.
The scaffold provided a stiff structure that supported growth of the mini lungs after transplantation while still allowing the transplanted tissue to become vascularized, growing blood vessels that supplied it with nutrients.
When the team examined the tissue, they found that it had not only survived, it had developed tube-shaped airway structures similar to the airways in adult lungs. It also developed mucus-producing cells, multiciliated cells and stem cells similar to those found in adult lungs.
“In many ways, the tissue grown in the study was indistinguishable from human adult tissue,” says senior study author Jason Spence, Ph.D., associate professor in the U-M Department of Internal Medicine and the Department of Cell and Developmental Biology at the U-M Medical School.
The researchers caution that they’re far from growing anything like a complete human lung—the tissue grown in the experiment was a mass of lung cells scattered among other types of cells inside the scaffold. But they say it’s an important early step that can yield valuable information about how healthy cells grow and develop. In the future, that could lead to new treatments for lung disease.
“What if we could regrow a portion of a damaged lung, like a patch?” Shea said. “Treatments like that, while challenging, may be possible.”
The lung tissue is one of several types of cultured organ tissue, or “organoids” that U-M research teams have developed—other cell types they’ve created include intestines, pancreatic cells and placenta cells. In addition to their uses in developing new cell-based therapy, Shea says the cells can provide a human model for screening drugs, studying gene function, generating transplantable tissue and studying complex human diseases like asthma.
“Organoids enable us to see the development and formation of an organ without having to conduct a test on an entire organism. And once we understand that, we can find new ways of repairing organs that are injured, or that haven’t developed properly.”
The paper is titled “A bioengineered niche promotes in vivo engraftment and maturation of pluripotent stem cell derived human lung organoids.” The research was supported by the National Institutes of Health (grant number R01 HL119215), by the NIH Cellular and Molecular Biology training grant at Michigan and by the U-M Tissue Engineering and Regeneration Training Grant.
- by Gabe Cherry, Senior Writer & Assistant Magazine Editor, Michigan Engineering
- Original Article: https://news.engin.umich.edu/2017/07/lab-grown-lung-tissue-could-lead-to-new-cancer-asthma-treatments/
by Kim Roth
The student-run organization M-HEAL, Michigan Health Engineered for All Lives, has a laudable, and ambitious, mission: to design healthcare solutions in collaboration with international partners to positively impact global health.
Today, with over 100 members on more than nine teams working on projects for communities worldwide, it’s no surprise M-HEAL has grown significantly over the past decade.
With growth has come increased interest among members to pursue the College’s Multidisciplinary Design Minor, which enables M-HEAL students to pursue academic credit for their project work. The trend has highlighted the need for additional mentorship to help students take their projects and products to the next level, so designs can be finalized, manufactured, and adopted by end users.
“Given the large number of design teams and students interested in the Multidisciplinary Design minor and the diversity of M-HEAL projects, students are best served if they can reach out to industry experts to help them navigate many of the key aspects of solution development – ideation, design, quality, risk management, and even business development,” says Aileen Huang-Saad, M-HEAL faculty advisor since 2007, assistant professor in biomedical engineering, entrepreneurship and engineering education.
The need has led to a budding mentorship program with medical device manufacturer Stryker Corporation. Following a successful pilot with Stryker Principal Engineer, Bill Hassler, and U-M mechanical engineering and design science graduate student, Michael Deininger, in the Winter 2016 semester, the program expanded quickly.
In Fall 2016, six Stryker engineering mentors – Bruce Henniges, Mitch Baldwin, CliffLambarth, Brian VanderWoude, SteveCarusillo and Dan McCombs – began working with several M-HEAL teams, offering dozens of students access to experts with industry experience and technical skills demanded by the complex design process. With the success of the program, M-Heal students added a local business mentor, Randy Schwemmin, in Winter 2017.
Teams typically meet with mentors via Skype every two weeks to discuss progress, challenges, and next steps. Both mentors and mentees are benefiting in big ways, and the model program is expanding to other industry participants as well.
“It’s so critically important our students have this input,” says Huang-Saad. “The more resources they can draw upon to help them design better products, the better they’re able to meet the needs of their intended end users. The teams’ mentors have helped them make great progress toward their respective goals.”
Stryker mentor Bill Hassler worked with Project MESA, a portable gynecological exam table for use in Nicaragua.
“Working with bright, motivated students who are doing good work for people who need help was an honor, and it was gratifying to see that my experience could have a positive impact and help them become even more knowledgeable and enthusiastic about their project,” – Bill Hassler
“Working with bright, motivated students who are doing good work for people who need help was an honor, and it was gratifying to see that my experience could have a positive impact and help them become even more knowledgeable and enthusiastic about their project,” says Hassler.
Getting to know those motivated, bright students also introduces the company to promising talent and aids recruitment efforts. “It’s a real win-win-win,” he adds. “The program has a very good vibe around here.”
Mission: To provide low-resource settings with a sustainable, user-friendly warming device to keep patients at a stable core body temperature during surgery while also reducing the risk of infection.
Mentor: Bruce Henniges
Next stop: Dominican Republic, May 2018
The team is currently prototyping and finishing the design of its second iteration warming device. Using input from clinical partners in the Dominican Republic, the team has been testing new ideas for the next prototype. The team’s regulatory group is investigating CE Mark designation and performing risk analysis, according to PeriOperative team member Hannah Soifer, rising senior and former M-HEAL secretary.
Team PeriOperative worked with Stryker mentor Bruce Henniges, senior director of advanced development, who helped with the risk analysis. “This was new territory for the team this semester, and Bruce spent a lot of time explaining the best way to go about conducting it,” says Soifer. He also helped the team with schematics to make a constant current source, “something we hadn’t known how to do before,” she adds.
Working with its Stryker mentor, the team “made faster progress because we were guided in the right direction from the get-go and our potential mistakes were caught early,” Soifer says. “Bruce brought an incredible knowledge base in all areas of design and development, and he always gave us advice or resources we hadn’t known about.”
Team: Project MESA
Mission: To design a portable gynecological exam table to help improve cancer screening and better monitor pregnancies in women at high risk of complications
Mentors: Dan McCombs, Cliff Lambarth, Randy Schwemmin
Next stop: Nicaragua, May 2017
The team is currently working on its sixth prototype. Members will return to Nicaragua this spring to meet with its clinical partners and get additional feedback on two prototypes, each with different features, so it can solidify the design. Members will also get feedback on two prototype tables it previously delivered, which have been in use with patients in-clinic, according to team member Samantha Fox, a rising junior.
During the 2016-’17 academic year, Stryker mentor Cliff Lambarth, senior principle engineering product manager, helped the team uncover some key design flaws and find solutions.
“He really forced us to think about design decisions we’d made and their justification. He analyzed our design – and pushed us to analyze it – and opened our eyes to changes we needed to make,” Fox says.
“His experience and technical knowledge made him able to immediately see things we didn’t, and he also emphasized justifying our decisions. We have really good documentation now of the decisions we made and why, and that’s going to help us move forward,” she adds.
Team: Solar Fridge
Mission: To design an absorption refrigerator that uses solar energy to help rural health clinics and traveling health workers keep vaccines at a consistent, desired temperature.
Mentor: Steve Carusillo
Next stop: Dominican Republic, August 2017
The team has been designing and building a prototype that could be built by users on site and running evaporation tests. Members will travel to the Dominican Republic this summer to conduct a needs assessment in a local community, recommended by M-HEAL alum Hope Tambala (Chemistry, ’15), now serving as a Peace Corps volunteer in the country.
The team worked with Stryker mentor Steve Carusillo, vice president of research and development technology, who has been helping the technical team test components and develop ideas for redesigning the device for the new stakeholder community, according to team member Michelle Ruffino, rising senior.
“It’s been a very valuable interaction,” Ruffino says. “About two weeks ago I was telling Steve about issues a sub-team was having – we’re not getting enough heat transfer from the copper pipe to the condenser – and he told us to try thermal epoxy. We bought some, tested it, and we’re very likely going to implement it. It’s inexpensive and easy to use. It’s that kind of real-world expertise and experience that helps us so much,” she adds.
Team: The Initiative
Mission: To reduce infant mortality with a low-cost warmer that combines kangaroo care with an infant incubator.
Mentors: Brian VanderWoude, Mitch Baldwin
Next stop: Ethiopia, August 2017
The team recently completed its third prototype, which includes a heated mattress, a bassinet, and a wearable wrap to hold the infant against the parent. Members plan to travel to Ethiopia this summer to further evaluate the hospital environment, conduct usability studies, and meet with its community partners.
Working with Stryker mentors “definitely helped speed up our project timelines,” said team lead Connor Yako. Mentors provided technical expertise, including feedback on materials and manufacturability, as well as big-picture input. “Having that industry experience helped us avoid power consumption and other problems we might have encountered down the line; it helped us pick the right paths early on.”
Excited by the opportunity to improve access to healthcare in a developing area of the world, Brian Vanderwoude, principal engineer with Stryker, said the team’s “creativity and resourcefulness were apparent” despite limited resources. “They weren’t intimidated by challenges, and they were really open to learning.”