Plastic Surgery Perspectives: Research—Interview with Dr. Paul S. Cederna

by Stav Brown, BS1

Sackler School of Medicine at Tel Aviv University, Tel Aviv, Israel

Through interviews with leaders in the field, we present here the second piece in the series “Plastic Surgery Perspectives” dedicated to providing residents and medical students a perspective on future career options and possible fellowships within the field.

This piece includes contributions from Dr. Paul S. Cederna.

Why did you choose this specific field of research?

I chose Plastic Surgery overall because I absolutely love the immense variety of clinical cases that we have. I love being able to incorporate the diagnostic skills of a surgeon with the technical virtuosity of a plastic surgeon to solve some of the most challenging problems. When I perform an operation, I can help one person at a time. When I work in my research laboratory, I can advance the field through innovation and discovery. In this way, I have the opportunity to help many people all at the same time. This is what has driven me to perform research. It is so satisfying to have this as a major component of my professional life.

My research efforts are focused on peripheral nerve regeneration and prosthetic control to enhance functional restoration following limb loss. When I was a young faculty member, I had a patient who was a national level power-lifter who moved an aluminum ladder into a high voltage line and got electrocuted. He experienced a 50% TBSA burn and an extensive burn involving his arm resulting in an amputation. I had operated on him many times to treat his burn injuries and to provide functional enhancement after his wounds were all healed. During this time, he shared with me all of his struggles performing activities of daily living. He detailed for me all of the things he could no longer do since having an arm amputation. He also shared with me the many challenges of his body-powered prosthetic device. This experience was very moving for me and drove me to want to do research in this area to not only make his life better, but also help all of the people just like him who have sustained limb loss. In this area of research, I was able to incorporate my biomedical engineering background with my surgical training in plastic surgery to try to solve this incredibly challenging problem, not only for this patient but for the millions of patients around the world who have sustained limb loss.

How has this field changed since you started?

When we started performing research in this area, the state of the art for prosthetic rehabilitation was the myoelectric prosthetics. Myoelectric prosthetics have two control sites, a flexor control site and an extensor control site. If you want to close the prosthetic hand, you fire your flexors and the hand closes. If you want to open the prosthetic hand, you fire your extensors and the hand opens. However, if you want to just flex your thumb, you have to click through programs, by firing your flexors and extensors at the same time, until you get to the thumb control mode. Once you get to the proper mode, then you fire your flexors and the thumb will flex. It is not at all naturalistic. That was, by far, the best thing available to provide people with a “functioning” hand. The myoelectric prosthetics didn’t work very well and did not provide naturalistic function, and as a result, many people abandoned them. They abandoned them because they were heavy, didn’t work very well, and the batteries didn’t last very long. Most people used body power prosthetics because they were quite functional. Even though this technology is hundreds of years old, it was the best we had at the time. Based on this, I was determined to give people a hand that looks normal, has individual finger control and provides sensory feedback. A prosthesis that would move naturally and would be embodied by the patient. If we could achieve that goal, it would be amazing. We are getting there.

What are your main interests in your field?

Our initial approach to provide high fidelity control of prosthetic devices was to create a tissue-engineered construct. The idea was that we would develop a peripheral nerve interface device that would allow us to record efferent motor action potentials and provide a site to create afferent sensory feedback. We focused on the peripheral nervous system since this is the location where many different functions are sorted and easily accessible. We would then harvest signals from the peripheral nerves and have the patient’s own peripheral nerves control the prosthetic device. All the efferent motor action potentials persist after an amputation so there was no reason we couldn’t record them and use them to control the prosthetic hand. Unfortunately, these signals are really tiny and the noise in the system is very big, so trying to record efferent motor action potentials is very challenging due to this unfavorable signal to noise ratio (small signal/big noise). Out concept was to interface with the peripheral nerves in a way that would provide a long term stable connection but would also amplify the efferent motor action potentials. This is where the concept of the regenerative peripheral nerve interface (RPNI) began. We would connect a small skeletal muscle graft to the end of the nerve, this muscle would get reinnervated by the nerve, and then we record the amplified EMG signals from the RPNI. Instead of trying to record nerve signals directly from a nerve, we would record small electromyography (EMG) signals from the muscle attached to the nerve. This RPNI was shown to dramatically amplify the efferent motor action potentials making a very favorable signal to noise ration (big signal/small noise). With this strategy, even if someone with limb loss is trying to make a small delicate movement with their prosthetic limb, we can record those signals because we have amplified them so much with the RPNI. Interestingly, we also discovered that when we created RPNIs on the ends of nerves, there were no neuromas forming. This was very exciting because not only could we control a prosthetic device with the RPNIs but we could also prevent neuroma pain and phantom pain in the patients. What a great opportunity to eliminate all of the painful sequelae of amputation experienced but so many patients with limb loss. This was completely novel and different than what anyone had done in the past.

Tell us about a clinical case/aspect that has influenced you or shaped your vision of the field.

We have performed a lot of research in animal models to be able to optimize the development of the regenerative peripheral interface. We then went through the FDA and got an investigational device exemption which allowed us to implant electrodes into our regenerative peripheral nerve interfaces (RPNIs) for control of a prosthetic device. One of the very first person we selected for this procedure was a young man who had lost his hand in an unfortunate 4th of July fireworks accident. He had horrible problems of phantom pain and neuroma pain, was taking large doses of narcotics and had many unsuccessful interventions, surgical and non-surgical, to try to treat his pain. We did RPNIs to help him with his pain. Postoperatively, he did incredibly well. He didn’t need his narcotics anymore, he was more active, he was leaving his house, he was able to wear his prosthesis. He asked if there was something else we could do for him and became our very first patient with RPNIs and implanted electrodes for individual finger control of a prosthetic hand. For the first time since his accident he had a hand that moved like a normal hand. It was a life changing experience for him. For us, it was incredibly gratifying knowing that all of the work we had done in the lab to get ready for this moment, worked out. For the first time we were seeing the spoils of our hard work in the lab. We were helping people, touching lives by providing them with an improved quality of life and giving them an opportunity to ultimately have hand that moved like a normal hand. We were improving patient’s lives… such an incredible feeling.

What role does technology play in your field of research?

The technology piece in our work is obviously a huge component. We have an incredible collection of really gifted people who we work with on a daily basis to develop this technology for use in humans. We have plastic surgeons, many different types of engineers including mechanical engineers who work on the creation of mechanical devices, electrical engineers that work on all the circuit boards to control the signals, material scientists who work on the materials that interface with the biologic tissues, information scientists who write the algorithms to interpret the signals that are going to control the device, and chemical engineers who work on developing novel materials to improve the fidelity of our control signals. When we bring this entire team together to focus all of our energies on solving one major problem, improving functional restoration and prosthetic rehabilitation for patients with limb loss. Each individual brings their expertise, knowledge, and skills to the team to allow us to accomplish so much more than any single individual could accomplish on their own. With this approach, we are making dramatic progress to improve the lives of patients with limb loss.

What most excites you when you anticipate the future of the field?

The thing that excites me most about the research we perform is that we have the opportunity to help millions of people suffering from amputations who have horrible neuroma pain and phantom pain. By performing RPNIs, we can reduce and, in many cases, eliminate this pain. In addition, we also have the opportunity to provide people with a prosthesis that moves like a normal hand and provides sensory feedback. It’s been 40 years since Luke Skywalker lost his hand in Star Wars and was given a hand that moved naturalistically. However, that was science fiction. 40 years later we are actually getting closer and closer to that. Anyone who saw the movie would have never dreamed that this would ever be possible. It could never happen. Well… now it’s actually happening and I am so excited because it’s going to help so many people.

For a resident interest in incorporating basic science into their clinical career, what advice do you have?

I think that anybody interested in research should pursue that dream. Plastic surgeons are an incredibly creative group of people who have the opportunity to apply all their knowledge and skills to solve some of the most challenging reconstructive problems. Plastic surgeons can think of things and can conceive of solutions that other people have never thought of before. We can bring those skills into this arena and change the world. On our case, people had been working for decades on interfacing with peripheral nerves, but no one ever thought that you could take a piece of a skeletal muscle graft and put it at the end of a nerve and use it as an amplifier of signals. It’s a simple concept for a surgeon, but it’s something that the people who have been working in this field for decades never thought of because they didn’t have the background that we have as plastic surgeons. Having the opportunity to take our skillset from plastic surgery and bring it into this world is incredible.

There are many people who say that if you’re a clinician you can’t be competitive for funding. I couldn’t disagree more. I think we have an unfair advantage, because we think of things that no one else has ever thought of before. We can attack problems in novel ways, and we can, through innovation, investigation, discovery and creativity make the world a better place, change people’s lives, advance the field forward and take the direction of our specialty to new areas. We can solve problems that no one has been able to solve. I encourage anyone interested in research to pursue that dream, because if they love it, they can make great things happen.

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