Nearly $60 million in grants, nine patents, and more than 200 manuscripts mark the University of Michigan's Regenerative Peripheral Nerve Interface (RPNI) program as it moves from bench to bedside through Blue Arbor Technologies.

The work began in 2007 when BME and Plastic Surgery professor Paul Cederna joined a U.S. Army Multidisciplinary University Research Initiatives (MURI) proposal with then-U-M BME professor Daryl Kipke. The team secured $4.5 million. Over 17 years, collaborators including Cindy Chestek (BME, Electrical Engineering and Computer Science, Robotics, Neurosurgery), Brent Gillespie (Mechanical Engineering, Robotics), David Martin (Material Science), and Deanna Gates (Movement Science) extended that initial investment into a portfolio Cederna calls "two breakthroughs in one program."

What did the program build?

The first breakthrough is surgical. RPNI prevents neuroma formation—a painful nerve growth after amputation—and simultaneously creates an interface that electrodes can read to control a prosthesis. "Our Regenerative Peripheral Nerve Interface (RPNI) procedure not only created a way to interface nerves with electrodes for prosthetic control, but we unexpectedly discovered it prevented neuroma formation," Cederna said. "This changed amputation care, and now RPNIs are performed worldwide."

The second covers prosthetic function. Algorithms and electrode interfaces now decode motor intent at the level of individual finger and wrist movements, and return sensory feedback from upper and lower limbs. "We've demonstrated control far beyond what current commercial prostheses provide," Cederna noted. Chestek's team built the machine-learning and AI pipelines that translate recorded nerve signals into prosthesis commands.

How did the science reach commercialization?

Three years ago, Blue Arbor Technologies CEO Tod Borton joined to shepherd the technology through regulatory and manufacturing milestones. "As I learned about the team's clinical success—both in eliminating neuroma pain and enabling sophisticated prosthetic control—I saw the potential," he said. The startup raised $4 million in pre-seed funding.

"The pre-seed funding we raised of $4 million was possible only due to the infrastructure and connections initially enabled by U-M and Coulter," Borton said. BME's Coulter Translational Research Partnership Program, now in its 20th year, backed both early prototype work and the regulatory strategy. "Coulter's role is to unite engineers and clinicians and drive research to focus on real patient impact," said Thomas Marten, Coulter's managing director. "Paul's work exemplifies this, with its two-pronged breakthrough."

Cederna credits Coulter for closing the gap between academic and commercial skill sets. "Establishing a business wasn't in my original skill set. Coulter, especially Tom Marten and the board, provided direction and were instrumental in helping to guide, mentor, and support us during our early phases of company formation and commercialization," he said. The program also connected the team to U-M's Fast Forward Medical Innovation and Innovation Partnerships units, which helped secure nine patents.

What does the patient pipeline look like?

RPNI surgery has reached the global clinic. Cederna cites hundreds of thousands of amputees who no longer develop neuroma or phantom limb pain thanks to the procedure. The addressable population remains large: 1.7 million Americans live with limb loss, and roughly 25 million patients in Asia face similar challenges.

• 2007: $4.5M Army MURI grant launches the program
• 17 years of NIH and Department of Defense support bring cumulative grants to roughly $60M
• 9 patents and over 200 manuscripts anchor the IP and evidence base
• December 2025: first RESTORE ESU implant goes ahead in Vienna, Austria
• Early 2026: U-M trials open, covering both pain prevention and prosthetic control

"Early 2026 will see trials at U-M—both aspects, focusing on pain prevention and prosthetic control—will reach more patients soon," Cederna said.

What does the team say about scaling translational work?

Cederna and Borton both stress adaptability. The Blue Arbor team revised its initial device design after internal debate over patient safety and regulatory fit. "Product development requires deep belief and humility," Borton said. "You must be ready to pivot, challenge assumptions, learn from failures, and keep patient needs central. Egos must be set aside."

Cederna added a sharper rule: "When something doesn't work, we adjust rapidly—sometimes, winners need to quit a failing strategy in order to succeed."

Marten wants the project's discipline institutionalized. "Blue Arbor sets an example within Coulter—document what works, and value adaptive decision making," he said. The Coulter Program enters its 20th anniversary year with this case study positioned as its flagship, and the Vienna implant converts a 17-year research arc into a countable clinical event.