A Better Way to Connect Arteries How Coulter’s Newest Licensed Product Is Making Its Way from the Classroom to the Clinic

When reconstructive surgeons repair a breast after mastectomy or a severely injured leg after a car accident, they often move tissue harvested from one part of the body to another using microsurgical techniques. A new device developed at U-M and supported by the Coulter Translational Research Partnership Program will make it possible to connect arteries in the transferred tissue to those at the repair site in just minutes with a few easy steps. The device, called the arterial everter, looks like a thin silicone pen with a flexible steel spine. It was developed as an accessory for the market’s leading product for connecting vessels, the GEM Microvascular Anastomotic Coupler from Synovis Micro Companies Alliance, enabling it to work as well on arteries as it currently does on veins.
The Arterial Everter & Synovis Coupler
The arterial everter was developed at U-M to allow Synovis’ GEM coupler to connect arteries as easily as it connects veins. To use the coupler, a surgeon slides two cut vessels through a pair of plastic rings, secures each vessel’s end to a series of metal pins, and then clips the rings together. The everter allows surgeons to spread the more muscular arterial walls over the rings and push them securely onto the pins. Credit: Jeffrey Plott

This enhanced usability has long been on many mircosurgeons’ wish lists because of the coupler’s speed, ease of use, and effectiveness in re-establishing venous blood flow from transplanted tissue. However, arteries’ more muscular walls have made them hard to maneuver on the coupler (see image above). This typically requires them to be meticulously hand-sewn and adds significant time to surgery.

Overcoming this barrier, say the everter’s developers, was made possible by the rich ecosystem of biomedical innovation at U-M – one that has taken the device down a carefully crafted pathway, from classroom challenge to Coulter project to industry license.

Bringing Your Problems to Class

This innovation began as an increasing number have in recent years – as a classroom project. U-M’s Plastic Surgery Section Chair Paul Cederna, MD, has long been familiar with the time-consuming and technically demanding nature of hand-sewing tiny, 1 to 3 millimeter arteries in complex tissue transfers. But he’s also a professor of biomedical engineering and knew this was an ideal problem for U-M’s engineering design students.

So, Cederna brought the problem to ENG 490/ME 450, a multidisciplinary design and manufacturing course co-taught by Mechanical Engineering Professor Albert Shih, PhD, to see what solutions might emerge. Cederna further upped the odds of success by convening a crack support team: Jeffrey Plott, then a PhD student in Shih’s lab, to serve as a product-development mentor, plus two fellow U-M plastic surgeons, Associate Professors Adeyiza Momoh, MD, and Jeffrey Kozlow, MD, for clinical guidance, prototype testing and feedback.

The team presented the problem, advised the students and was soon rewarded with a number of potential solutions. By the course’s end, the leading contender could successfully evert artery walls over Synovis’ existing coupler.

Though a breakthrough in function, the design developed in class involved more moving parts than was ideal in the operating room. But, in it, the team saw the seeds of a winning device. With input from the surgeons and students, Plott continued streamlining the concept. When he arrived at a pen-like tool that could spread the cut end of an artery and affix it to the coupler, the team knew they were onto something.

 

Developing the Everter
The challenge with using the coupler on arteries is that their muscular walls are hard to spread over the device’s rings, often popping off one anchoring pin as the next is attached.
In the class design, a catheter balloon stabilized the artery while a plunger-type tool (yellow) pushed its ends onto the coupler pins all at once. Credit: ENG 490 student team The next version was a rigid plastic tool with a telescoping dilation mechanism and channels that could accept the coupler’s pins with a single push. Though streamlined, it required precise surgical alignment to avoid bending the pins. Credit: Jeffrey Plott The latest design is a flexible tool with a tapered silicone tip that can spread the artery onto the coupler’s pins from almost any angle. The pins pierce through the artery and into the silicone without bending, and the tool’s shaft can be angled as needed. Credit: Carolyn McCarthy

Tapping Coulter, Engaging Industry

Cederna approached his contacts at Synovis to gauge their interest in a product with the potential to enhance the coupler’s usability and – since it would now be ideal for both types of vessels – boost its sales. With their interest piqued, his next call was to Coulter.

“I’d worked with Coulter in the past and knew our team would benefit from their expertise in translating products to the clinical arena,” says Cederna. “I also knew we’d need funding for animal studies to confirm the device could do what we thought it could do.”

Recognizing the everter’s potential, Coulter took the unusual step of submitting the project for approval outside its traditional funding cycle. “This project was unique in a number of ways,” says Managing Director of U-M’s Coulter Program Thomas Marten. “It offered a simple, elegant solution to a clear clinical need. It was an accessory to an existing, market-leading device. And it promised to improve patient care, reduce time under anesthesia and decrease surgical costs. With all this and an industry partner engaged, we were eager to maintain the team’s momentum.”

Coulter approved the project, and its funding allowed Plott and the team to further refine their prototype, generating a device that was easy to both use and manufacture. They knew they’d nailed it when the team connected model arteries in minutes.

Coulter also helped the team engage with Synovis and its parent company, Baxter, to design a pilot animal study to provide the safety and efficacy data the company would need to consider licensing the everter.

The resulting Coulter-funded trial involved plastic surgeons Adeyiza Momoh and Ian Sando, MD, in cutting and reconnecting the femoral arteries in a large-animal model, one side using the everter-coupler combination and the other using traditional hand-suturing. After the initial cases showed that the everter-coupler technique attached the vessels securely without damaging their walls, maintained unobstructed blood flow, and reduced procedure time from more than 20 minutes to just five, Coulter invited representatives from Synovis and Baxter to see the results.

“That was a big day for us,” says Synovis President Michael Campbell. “It’s one thing when you see an idea on the blackboard; it’s another to see that it works. We were excited.”

So much so, that with support from the U-M Office of Technology Transfer, Synovis has just licensed the everter and plans to continue developing it for market.

Product of an “Innovation Ecosystem”

The everter is a great example of how multiple aspects of the U-M environment can come together to support biomedical innovation, says Bryce Pilz, director of licensing for the Office of Technology Transfer. “Projects at U-M benefit from schools that are top in their respective areas, have great researchers, and have also invested heavily in commercializing research, with programs like Fast Forward Medical Innovation at the Medical School, the Center for Entrepreneurship at the College of Engineering, and the Coulter Program that spans both.” Along with Tech Transfer, these programs are part of a rich support system that educates faculty about commercialization and helps develop projects to the point that they’re ready for industry.

Coulter is a critical component of U-M’s biomedical innovation ecosystem that helps educate faculty about commercialization and develop projects to the point that they’re ready for industry.

Coulter’s role in this ecosystem is offering financial resources, connections and expertise in product development and regulatory planning to help investigators evaluate their technology’s market potential and develop a product that will be attractive to investors.

“With the everter,” says Pilz, “Coulter helped the team engage Synovis in preclinical research to de-risk the technology to the point that the company was prepared to license it and invest its own resources in getting the product cleared by the FDA and into the marketplace.”

Such support is essential, says Paul Cederna, in bridging the vast but underappreciated gap between an idea or device developed in the academic world and one that is teed up for industry. “Programs like Coulter are essential in helping us span the ‘valley of death,’ where you’ve created something that works beautifully in the lab but dies while you’re trying to get it into the clinic,” he says. “They not only fund experiments, but things like market analyses and business plan development – activities that granting agencies just don’t invest in.”

It’s this kind of support, he says, that combines with U-M’s extensive collaborations across medicine and engineering to make biomedical innovations like the everter possible.

Results from the everter study were recently published in the Journal of Reconstructive Microsurgery. In addition, the device has won national recognition in the Create the Future Design Contest and with a Baxter Young Investigator Award.

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Funding for the arterial everter was provided by the Coulter Translational Research Partnership Program. The program provides funding, expertise, and comprehensive support to accelerate the development of U-M technologies into new products that improve health care. Details at: coulter.bme.umich.edu.

U-M Schools and Colleges Form Regenerative Medicine Collaborative

March 31, 2017

ANN ARBOR, MI –A Regenerative Medicine Collaborative, formed with support from U-M Office of Research, College of Engineering, and School of Medicine, aims to foster connections and enable new initiatives among investigators at the major U-M schools and colleges, including: U-M Engineering, Medical School, Dentistry, LSA, Public Health, and Pharmacy.

The University of Michigan Office of Research charged a planning task force to evaluate The University of Michigan’s strength in regenerative medicine. U-M ranks #5 in the world for regenerative medicine related citations and the stakeholder group has received nearly $320 million from NIH over the last five years for related research. We are among the leaders in the number of patents awarded, with faculty interested in regenerative and restorative medicine submitting over 320 invention disclosures resulting in greater than 120 patent filings in the past five years.

A web site (http://regenerativemedicine.umich.edu) and monthly highlights aim to communicate the breadth and depth of regenerative medicine work being done at U-M. Furthermore, the regenerative medicine collaborative will solicit a call for themes to identify areas in which U-M can grow or lead an area. The initiative will, also, facilitate the assembly of teams to be competitive for large-scale initiatives and projects across disciplines.

In addition to the website and monthly highlights, a launch symposium is being planned for the summer of 2017 to welcome the stakeholders. If you are interested in receiving the newsletters or attending the symposium, please send an email request to Amalia DiRita (amdirita@umich.edu).

U-M, colleges team up in biomedical science teaching and learning

By Kara Gavin
UMHS Department of Communication

They’re at two different ends of the higher-education journey: some just starting out on associate’s degrees, others finishing up advanced training after earning a doctorate in biomedical science.

But there’s a lot they can teach one another, with the help of their professors.

Through a new five-year National Institutes of Health grant totaling $3.64 million, the two types of “learners” will come together for science and engineering education two southeast Michigan colleges.

Henry Ford College and the Wayne County Community College District have signed on to allow U-M Medical School and College of Engineering postdoctoral fellows to co-teach in their classrooms, working alongside their faculty.

The postdocs, who specialize in the fields of physiology and biomedical engineering, will hone their teaching skills with the help of HFC and WCCCD faculty mentors over four years. By planning and teaching a course together, the postdocs can prepare to teach and mentor students when they obtain their first faculty jobs.

Meanwhile, the associate’s degree students will receive team-based teaching from the U-M postdocs and the partner college’s faculty member in their engineering and science classes. The students will also have a chance to learn about scientific careers directly from a working research scientist, and to apply for summer experiences working in the same U-M research laboratory as the postdoc.

The program, called Institutional Research and Academic Career Development Award, builds on initial seed funding provided by the Office of the Provost and the deans of CoE and the Medical School coupled with a pilot program at HFC and WCCCD. With the new grant, U-M will be able to select three postdocs each year for a four-year stint that will involve teaching, research and mentoring by participating faculty.

The new grant makes U-M the 22nd site in a nationwide network of IRACDA centers funded by the National Institute of General Medical Sciences over the past 15 years. The program aims in part to address a longstanding lack of diversity in scientific careers.

Both of the colleges in the partnership have a high percentage of students who are from backgrounds that are underrepresented in science. Some of the U-M postdoctoral fellows chosen for the program will also be from such backgrounds, but all those chosen will be committed to careers working with such students.

Neuroscientist Victor Cazares and computational physiologist Wylie Stroberg have already been chosen as the first two U-M IRACDA fellows. Candidate trainees at U-M and other institutions nationally will be able to apply for enrollment on an annual basis in what is expected to be highly competitive positions.

More marketable skills all around

“For any postdoctoral fellow, having extra training in teaching skills gives them a leg up as they go on the job market, and we have fantastic partners at HFC and WCCCD to help our fellows enhance their teaching skills,” says one of the leaders of this effort, Dr. Bishr Omary, H. Marvin Pollard Professor of Gastroenterology, professor and chair of molecular and integrative physiology, and professor of internal medicine. “Through this program, they’ll not only develop those skills, but have a chance to inspire the next generation of potential biomedical researchers and research staff.”

David Sept, professor of biomedical engineering, who co-leads the program, notes that NIH statistics show IRACDA fellows were more productive scientifically than traditional postdocs.

In the pilot phase of the U-M program, which provided the data needed to apply for NIH funding, both the mentors at HFC and WCCCD and the participating postdocs expressed how pleased they were with the opportunity.

“The feedback we’ve gotten from the teaching mentors has been really gratifying,” says Sept. “And the postdocs tell us that it opened their eyes, and made them feel that they were really making a difference. They enjoyed it beyond their expectations.”

He notes that IRACDA fellows and community college faculty will collaborate to review existing curriculum and seek opportunities to include current scientific research to the college courses.

Janice Gilliland, associate dean of the Math and Science Division at HFC, said, “HFC is excited to be collaborating on the first IRACDA grant in Michigan. Our faculty have a great deal of pedagogical knowledge and classroom experience that they can share with the post-docs from U-M while at the same time having the chance to update themselves with current science research.”

“This is a very exciting opportunity,” said WCCCD Chancellor Dr. Curtis L. Ivery.  “This partnership opportunity with the U-M is consistent with our mission in developing students at all levels both in the classroom at the community college and for postdoctoral fellows. Such partnerships are essential to maximizing opportunities for our students in the greater Wayne County region.

“We’re very excited to be one of the inaugural community college partners and provide opportunity to hone teaching skills in the sciences for better effectiveness in the classroom where learning begins.”

Many students in colleges like HFC and WCCCD know about health professions from exposure to the health care system. But few have learned about the many career options available in academic and industry settings for people with science and engineering training. In the pilot phase of the program, the U-M fellows found themselves peppered with questions from students who were curious about their research and how they got into a scientific career.

The new program adds to U-M’s existing efforts to help postdoctoral fellows prepare for careers in academia, industry, government and more. The Center for Research on Learning and Teaching, which offers many teaching and learning workshops and seminars, is a co-supporter of the IRACDA effort.

The HFC and WCCCD faculty taking part in the IRACDA effort will also have an opportunity to participate in professional development activities at U-M, such as those offered through CRLT. Though most have doctorate degrees in their chosen fields, and many completed postdoctoral training, their laudable choice to focus on teaching in the community college environment means they may have fewer chances to connect with the research world they once trained in.

Source: http://record.umich.edu/articles/u-m-colleges-team-biomedical-science-teaching-and-learning