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.


The U-M-Coulter Partnership A pivotal program helps catapult promising biomedical technologies from the lab to the marketplace

by Aimee Balfe

The 1990s saw the rise of a new term that would reshape biomedical engineering and academic medicine in the years to come — “translational” research.

Driven by funders’ desire to bridge a gap between basic research and clinical application, it encouraged biomedical scientists to more directly impact human health by taking their work “bench to bedside.” In doing so, it suggested that the end-game for academics could just as reasonably be a high-impact journal article as a medical product poised for commercialization.

Perhaps no program at U-M played a greater role in institutionalizing this approach within the College of Engineering (CoE) and Medical School than the Coulter Translational Research Partnership Program.

Launching a Program – and a Mindset

The process began in 2005, when then-BME Department Chair Matthew O’Donnell led a successful pitch to the Wallace H. Coulter Foundation for its $5 million Translational Research Partnership Award in Biomedical Engineering.

The award supported research teams co-led by engineers and clinicians in developing promising health-related technologies that could be translated from the lab to the clinic via the marketplace. It offered individual project grants within a coaching framework designed to help participants think early-on about their technology’s path to commercialization.

“I was personally very excited about Coulter,” says O’Donnell. “It allowed me to marry my two loves, industry and academics. I thought how wonderful, especially for our junior faculty, to be exposed to a world where you don’t just write papers; you put out a device…that people will actually use in the clinic.”

“I thought how wonderful, especially for our junior faculty, to be exposed to a world where you don’t just write papers; you put out a device…that people will actually use in the clinic.”Matthew O’Donnell

O’Donnell’s enthusiasm spread quickly among the faculty and was sustained by his successor, Douglas Noll. In its first five-year funding cycle, the U-M Coulter Program supported 19 projects ranging from engineered ACL replacements to optical detection of pancreatic cancer to custom, 3D-printed biodegradable scaffolds for skeletal reconstruction and bone regeneration. The work yielded four start-up companies that garnered $25 million in funding. But just as importantly, the award provided a mechanism for cooperative translational research between the CoE and Medical School — an approach that was reinforced in 2012 when Biomedical Engineering became a joint department of both entities.

Endowment and Enhanced Support

The program’s success also positioned U-M for an even larger award — $10 million from the Coulter Foundation that was matched by the CoE and Medical School, yielding a $20 million endowment to support translational projects in biomedicine. U-M was one of only six universities nationwide to receive this award.

That was in 2011. Since the endowment, the Coulter Program has funded another 30 projects (see examples) and has ramped up its coaching in an effort to ensure the technologies it supports stand the best chance of making it to market through a license to an established company or start-up.

“Coulter is so much more than a funding entity,” says Tom Marten, managing director of U-M’s Coulter Program. “We’ve evolved to the point where we now guide projects through the same elements of new product strategic planning and development that are used in industry.”

“Coulter is so much more than a funding entity…We’ve evolved to the point where we now guide projects through the same elements of new product strategic planning and development that are used in industry.” Tom Marten

This happens even before funding decisions are made. Coulter has recently launched a program for its finalists, called the Coulter College Commercializing Innovation planning program, or C3i. It provides expert analyses of each project’s regulatory and competitive landscape, as well as market research in which target users evaluate the proposed product. The program also leads each team through eight weeks of structured homework guided by industry mentors matched to their project.

The result of this work is a “blueprint report” for each project that systematically examines its potential market; likely challenges; characteristics necessary to be sustainably adopted; as well as the research, intellectual property, and other milestones that must be met to make the product attractive to investors.

“By the time we go through this process, both Coulter and the teams have a clear sense of their project’s commercialization potential,” says Marten. This robust planning also means that the winning teams are able to hit the ground running, using their funds to implement the strategy they developed, and pressure-tested, through C3i.

Of course, all of this is possible because of Coulter’s reach and deep connections. “We have relationships with top industry executives, medical device serial entrepreneurs, regulatory specialists, and venture capitalists — many of whom are on our oversight committee — so we can provide expert mentoring to help faculty reach their hand-off goals.”

The projects funded since the endowment have yielded 7 start-ups, $30 million in outside investment and one license to industry. But Marten believes that with U-M’s talent pool, its culture of collaboration and innovation, and the resources provided by the Coulter Program, Tech Transfer, MICHR and others, there is even more success to come.

Highlighted Projects:


HistoSonics

Non-Invasive Precision Surgery

One of the earliest Coulter-supported projects involves histotripsy, a non-invasive surgical technique that uses the mechanical, not thermal, properties of focused ultrasound to precisely destroy target tissue without damaging surrounding structures. Coulter catalyzed a team of academics and businesspeople that launched a start-up around the technology and supported an intellectual property analysis that helped attract venture capital. The company, HistoSonics, has since secured more than $25 million in funding, developed a prototype device, conducted first-in-human clinical trials for enlarged prostates, and is now pursuing additional applications, such as liver cancer.

Slit-Stent

Lacrimal Drainage Device

One of Coulter’s more recent projects aims to help patients with excessive tearing. Traditional treatment involves creating and temporarily stenting a new drainage canal. But current stents don’t drain, so symptoms persist until the stent is removed months later. The Coulter program connected U-M oculoplastic surgeon Alon Kahana, MD, with Jeffrey Plott, a PhD student in ME/BME Professor Albert Shih’s lab. Plott solved the problem in a single day by cutting slits at key places in an existing lacrimal stent to create a patentable new “Slit-Stent” concept. The Coulter team, Kahana, and Plott are now collaborating with a leading manufacturer of lacrimal stents to modify one of their existing FDA-approved stents to create the Slit-Stent. The manufacturer has committed to running this product through its FDA-validated pre-clinical testing processes, which is required for an investigational device exemption (IDE) that U-M will file with the FDA. With the IDE in place, Coulter will fund a Slit-Stent clinical trial at U-M in late 2017 to generate the proof-of-concept data needed for a licensing arrangement.

NeuromaMend

Surgical Tool to Treat Neuromas

While working on a way to amplify nerve signals for prosthetic limb control, a U-M team that included BME Assistant Professor Cindy Chestek, PhD, and Plastic Surgery Section Chair and BME Professor Paul Cederna, MD, discovered a technique to treat neuromas. Neuromas are disorganized bundles of nerves that form when a nerve is severed; amputees suffer greatly from them, and they’re notoriously difficult to treat. However, Cederna developed a manual surgical procedure to wrap the severed nerves in a “cap” of harvested muscle tissue to relieve the pain. To make the procedure widely available, he sought a way to make it less time- and skill-intensive. Coulter funded development of a surgical device prototype that automates the procedure and allows surgeons to harvest the muscle, grab the nerve, and slide the muscle over the nerve in as little as five minutes. With support from Coulter, the team was able to demonstrate the functionality of the device in animal studies and secure a licensing agreement with Michigan-based RLS International. RLS will finalize development, and it hopes to file for FDA approval and bring the tool to market within two years.


Have A Great Biomedical Innovation That Could Improve Patient Care? Apply to the Coulter Program beginning Nov. 1st 2016

The UM Coulter Translational Research Partnership Program “Coulter Program” is pleased to announce the 2017 Call for Proposals.

 

Proposals will be accepted beginning November 1, 2016. The deadline for proposal submission is February 15, 2017.

 

The Coulter Program funds collaborative translational research projects between Engineering and Clinical faculty co-investigators. The goal of the program is to accelerate development and commercialization of new medical devices, diagnostics, and other biomedical products that address unmet clinical needs and lead to improvements in healthcare. Projects are actively supported and mentored by Coulter Program Management and a team of industry-experienced experts who proactively work to accelerate Coulter Program objectives. Coulter Program objectives and metrics for success involve developing new product concepts to the point of partnering with industry or forming start-up companies with follow-on investor funding to commercialize new products envisioned from translational research efforts. Coulter funding (typically $100,000 range for 1 year) does not require a departmental funding match or cost-sharing of salaries.

 

Distinctive aspects of the Coulter Program include business assessment work that dovetails with technical milestones for each project. Specific benefits to each project include:

  • New product planning support
  • Business development support
  • Market research
  • Regulatory guidance
  • Follow-on funding guidance
  • Mentorship from the Oversight Committee
  • The C3i Commercialization Planning Program

 

For more information, visit http://www.bme.umich.edu/coulter or download Coulter proposal instructions and application forms here: http://bme.umich.edu/research/coulter/process/apply/

 

For questions, please contact Thomas Marten, Coulter Program Director, at tmarten@umich.edu or (734) 647-1680.


UM Coulter Translational Research Partnership Program Awards 4 Projects for 2016-2017 Funding

The UM Coulter Translational Research Partnership Program “Coulter Program” is pleased to announce its funding selection for FY 2017.

The Coulter Program funds translational research projects between Engineering and Clinical faculty co-investigators. These projects aim to develop medical devices or other biomedical products with the goal of new company formation or a technology license to industry partners. Throughout the funding period and beyond, teams receive a high level of guidance and support for new product planning, market opportunity evaluation, patent filing, prototype development, regulatory strategy planning, and sourcing for follow-on funding or licensing.

For the FY 2017 funding cycle, four projects were selected for funding:

Cryo-Anesthesia for Intravitreal Injections

Current anesthetic procedures prior to intravitreal injections are uncomfortable and painful for patients, increase procedure time, and can increase the occurrence of ocular surface bleeding. Retinal Specialist Cagri Besirli, MD, PhD, and Mechanical Engineer Kevin Pipe, PhD, have developed a handheld device that delivers thermoelectric, contact cooling to the ocular surface as a rapid anesthetic for performing painless intravitreal injections in less time. This project also received Coulter funding last year for the  FY16 cycle. During their first year of Coulter funding, the team developed their first prototype and conducted device safety testing to determine optimal parameters for safe use. The team received IRB approval for a first-in-human (FIH) study which they initiated at the Kellogg Eye Center. With this second year of Coulter funding, the team will refine their current prototype using FIH study outcomes, design for manufacturability changes, and professional market research feedback. Regulatory consultation leading to a Pre-Submission meeting with the FDA will pave the way to a second clinical study funded by Coulter to demonstrate improved patient-reported outcomes and reduced anesthesia times compared to standard-of-care anesthesia methods. This project will likely lead to an exciting start-up company to commercialize the device.

 “Slit-Stent” Lacrimal Drainage Device for the Treatment of Epiphora Due to Insufficient Drainage

Oculoplastic surgeons treat epiphora, or excessive tearing, by surgically creating a new tear drainage system and placing a lacrimal stent to allow healing. Current stents take up space in the newly created tear drainage system, and patients do not experience relief from epiphora until the stent is removed 3-6 months later. Oculoplastic Surgeon Alon Kahana, MD, PhD, teamed up with Mechanical Engineers Albert Shih, PhD and Jeffrey Plott, to develop the “Slit-Stent”, a lacrimal stent constructed to facilitate drainage of tears through the stent after placement, which will provide patients immediate symptomatic relief. With Coulter funding, the team will pursue an Investigational Device Exemption (IDE) and conduct a clinical study to demonstrate that “Slit-Stent” provides improved symptomatic relief from epiphora while maintaining mechanical integrity and having no significant difference in infection risk compared to standard stents. Positive clinical study outcomes will provide a strong position for licensing of the technology to an existing ophthalmic medical device company.

Dynamic Arterial Morphology Analysis for Prediction of Intradialytic Hypotension

Intradialytic hypotension (IDH), a drop in blood pressure that cannot be compensated for by vasoconstriction, occurs in 20-30% of all hemodialysis sessions. This sometimes leads to session abandonment and fluid overload as patients are not able to be adequately dialyzed. Emergency Medicine Physician Kevin Ward, MD, Mechanical Engineer Kenn Oldham, PhD, and Computational Medicine and Bioinformatics Associate Professor Kayvan Najarian, PhD, have developed a small, wearable, noninvasive monitor that predicts the onset of IDH during hemodialysis and provides a warning to dialysis clinic staff, allowing them to implement countermeasures to prevent the hypotensive episode and continue the dialysis session. With Coulter funding, the team will build prototype devices to obtain clinical data on patients undergoing dialysis in the U-M Acute Dialysis Unit to refine and optimize the prediction algorithm. The goal of the study is to demonstrate the ability to predict IDH within 2 minutes of onset with 80% sensitivity and specificity. Positive results from this clinical study on the ability to predict IDH will greatly accelerate development and licensing to a commercial partner.

Miniaturized HemoRetractoMeter (mHRM) Blood Coagulation Diagnostic

Blood coagulation is a critical hemostatic process that must be properly regulated to maintain the delicate balance between bleeding and clotting. Coagulation diagnostics using whole blood thromboelastography measurements are rapidly gaining clinical acceptance, but commercially available systems are significantly limited by their size, cost, inter-assay variability, and significant user intervention. Emergency Medicine Physician Kevin Ward, MD and Mechanical Engineer Jianping Fu, PhD, have developed a small, inexpensive, easy-to-use and maintain, near point-of-care whole blood thromboelastography device (mHRM) that provides equivalent results to commercially available thromboelastography devices in less time. With Coulter funding, the team will improve the mHRM manufacturing method, conduct clinical testing to verify mHRM reliability on samples with known coagulation profiles, and demonstrate equivalency of the mHRM to commercially available thromboelastography devices. Positive results from this clinical study will strongly position this technology for commercial partnering with existing companies in the coagulation monitoring space.

See http://bme.umich.edu/research/coulter/ for more information about these newly funded projects. For more information about the Coulter Program, contact Thomas Marten, Coulter Program Director, at tmarten@umich.edu.  Look for the next Coulter Call For Proposals in late Fall 2016.