How biomechanics can impact medicine – Interview with Jay Humphrey

[dropcap]I[/dropcap]t is a love for mechanics and mathematics, as well as an intense interest in biology and health, that led Jay Humphrey towards the field of biomechanics. Right after his PhD from the Georgia Institute of Technology in Engineering Science and Mechanics, in 1985, he pursued post-doctoral training in cardiovascular research at The Johns Hopkins University School of Medicine. Now a researcher at Yale University, his pioneering research in the field helps predict and understand aortic aneurysms and dissections. On 29 June this year, IMT awarded him the honoris causa title for this groundbreaking work and the projects he undertook with Mines Saint-Étienne. On this occasion, I’MTech asked him a few questions about his vision on biomechanics, his perception of his work, and how he thinks his community impacts medicine.

How would you define the field of biomechanics?

Jay Humphrey: A general definition of biomechanics is the development, extension, and application of mechanics to study living things and the materials or structures with which they interact. For the general public, however, it is also good to point out that biomechanics is important from the level of the whole body to organs, tissues, cells, and evens proteins! Mechanics helps us to understand how proteins fold or how they interact as well as how cells and tissues respond to applied loads. There is even a new area of application we call mechanochemistry, where scientists study how molecular mechanics influences the rate of reactions in the body. Biomechanics is thus a very broad field.

With protein and tissue studies, biomechanics seems to have a very modern dimension, doesn’t it?

JH: In a way, biomechanics dates back to antiquity. When humans first picked up a stick and used it to straighten up, it was biomechanics. But the field as we know it today emerged in the mid 1960’s, with early studies on cells — the red blood cells were the first to be studied. So, we have been interested in detailed tissue and cells mechanics for only about 50 years. Protein mechanics is even newer.

Why do you think the merger between mechanics and biology occurred in the 60’s? Has there been a catalyst for it?

JH: There are probably five reasons why biomechanics emerged in the mid 60’s. First, the post-World War II era included a renaissance in mechanics; scientists gained a more complete understanding of the nonlinear field theories. At the same time, computers emerged, which were needed to solve mathematically complex problems in biology and mechanics — this is a second reason. Third, numerical methods, in particular finite element methods, appeared and helped in understanding system dynamics. Another important reason was the space race and the question, ‘How will people respond in outer space, in a zero-gravity environment?’, which is fundamentally a biomechanical question. And finally, this was also the period in which key molecular structures were discovered, like that for DNA (double helix) or collagen (triple helix), the most abundant protein in our bodies. This raised questions about their biomechanical properties.

So technological breakthroughs definitely have played an important part in the development of biomechanics. Are recent advances still giving you new perspectives for the field?

JH: Today, technological advances give us the possibility to perform high-resolution measurements and imaging. At the same time, there have been great advances in understanding the genome, and how mechanics influence gene expression. I have been a strong advocate of relating biomechanics – which relies on theoretical principles and concepts of mechanics – to what we call today mechanobiology — how cells respond to mechanical stimuli. There has been interest in this relationship since the mid 70’s, but we have only understood better the way a cell responds to its mechanical environment by changing the genes it expresses since the 90’s.

Is interdisciplinary research an important aspect of biomechanics?

JH: Yes, biomechanics benefited tremendously from interdisciplinarity. Many fields and professions must work together: engineers, mathematicians, biochemists, clinicians, and material scientists to name a few. And again, this has been improved through technology: the internet allowed better international collaborations, including web-based exchanges of data and computer programs, both of which increase knowledge.

Would you say your partnership with Stéphane Avril and Mines Saint-Étienne is a typical example of such a collaboration?

JH: Yes, and it is interesting how it came about. I have a colleague in Italy, Katia Genovese, who is an expert in optical engineering. She developed an experimental device to improve imaging capabilities during mechanical testing of arteries. We worked with her to increase its applicability to vascular mechanics studies, but we also needed someone with expertise in numerical methods to analyse and interpret the data. Hence, we partnered with Stéphane Avril who had these skills. The three of us could then describe vascular mechanics in a way that was not possible before; not one of us could have done it alone, however, we needed to collaborate. Working together, we developed a new methodology and now we use it to better understand artery dissections and aneurysms. For me, the Honoris causa title I have been awarded recognizes the importance of this international collaboration in some way, and I am very pleased for that.

Including this research on aneurysms and cardiovascular system description as well as everything else that you have worked on, what is your scientific contribution that you are the proudest of today?

JH: I am proud of a new theory that we proposed, called a ‘constrained mixture theory’ for soft tissue growth and remodelling. It allows one not only to describe a cell or tissue at its current time and place, but also how it can evolve, how it will change when subjected to mechanical loads. The word ‘mixture’ is important for tissues consist of multiple constituents mixed together: for example, smooth muscle cells, collagen fibers, and elastic fibers in arteries. This is what we call a mixture. It is through interactions among these constituents, as well as through individual properties of each, that the tissue function is achieved. Based on a precise description of these properties, we can describe for instance how an artery will be impacted by a disease, and how it will be altered due to changes in blood circulation. I think this type of predictive capability will help us design better medical devices and therapeutic interventions.

Could it be a game changer in medicine?

JH: ‘Game changer’ is a strong word, but our research advances definitely have some clear clinical application. The method we developed to predict where and when a blood clot will form in an aneurysm has the potential to better understand and predict patient outcome. The constrained mixture theory could also have real application in the emerging area of tissue engineering. For example, we are working with Dr. Chris Breuer, a paediatric expert at Nationwide Children’s Hospital in Columbus Ohio, on the use of our theory to design polymeric scaffolds for replacing blood vessels in children with congenital defects. The idea is that the synthetic component will slowly degrade and be replaced by body’s own cells and tissues. Clinical trials are in progress in the US, and we are very excited about this project.

These are really concrete examples of how biomechanics research can lead to significant changes in medical operations and processes. Is it a purpose you always had in mind through your career?

JH: About seven years ago, my work was still fundamental science. I then decided to move to Yale University to interact more closely with medical colleagues. So my interest in clinical application is recent. But since we are talking about how biomechanics could be a game changer, I can give you two major breakthroughs made by some colleagues at Stanford University that show how medicine is impacted. Dr. Alison Marsden uses a computational biomechanical model to improve surgical planning, including that for the same tissue engineered artery that we are working on. And Dr. Charles Taylor has started a new company called HeartFlow that he hopes will allow computational biomechanics to replace a very invasive diagnostic approach with a non-invasive approach. There is great promise in this idea and ones like it.

What are your projects for the upcoming years?

JH: I plan to focus on three main areas for the future. First is designing better vascular grafts using computational methods. I also hope to increase our understanding of aneurysms, from a biomechanical and a genetic basis. And third is understanding the role of blood clots in thrombosis. These are my goals for the years to come.