Soslowsky Sentiments: H. R. Lissner Medal Presentation

This article generally reproduces the presentation given by the author at the 2018 World Congress of Biomechanics in Dublin, Ireland in recognition of his receipt of the H.R. Lissner Medal from the American Society of Mechanical Engineers. This paper discusses my family, followed by my undergraduate and graduate experiences at Columbia University. It then reviews some activities during my first faculty position at the University of Michigan and then continues on with my experiences over the past 20+ years at the University of Pennsylvania. I review the programmatic approaches I have taken that have resulted in a publication history in different, but related areas, as well as future plans. I describe the graduate students, other trainees, staff, and environment that have made my efforts so enjoyable and gratifying. I then note some of the additional leadership positions I have had the good fortune to experience along the way thus far. I conclude by speaking briefly about my close partners and mentors, as well as some key takeaways from my experience.

I am truly humbled and honored to receive this award. I begin by acknowledging and recognizing the amazing history of H. R. Lissner Medal recipients starting in 1977 and going through the present (Table 1). This list represents a literal “who's who” in the field of biomechanics and to think my name will join that list feels a bit strange. I would like to call special attention to three of the previous recipients because they each played a central role in my professional development and I will discuss them in this paper: first, Richard Skalak (1985) for whom I worked as an undergraduate student; second, Van Mow (1987) my Ph.D. thesis advisor; and third, Steve Goldstein (2005) who hired me for my first tenure track faculty position.

I want to start by acknowledging my family. My parents Phyllis and Martin shown here at their wedding in 1959 (Fig. 1) have been amazing pillars of strength, love, and support for me in everything that I have tried to do from my earliest memories. My parents and my sister Sandy formed a very loving and nurturing household (Fig. 2). I am truly lucky to have grown up with this amazing family.

My undergraduate experience was at Columbia University in New York and I had the great fortune to meet Professor Richard Skalak at the beginning of my sophomore year in 1983. Professor Skalak was the James Kip Finch Professor and Director of the Bioengineering Institute at Columbia (this was long before there was a Department of Biomedical Engineering). He hired me then as his first work-study student and I began working in his office for a part-time job (I worked in the main university library as a freshman). My experience with Professor Skalak was my greatest opportunity and fortune. When people ask me how and why I am in the field, my answer is simple. For many, the answer is multifactorial. It was a personal injury that got me interested, coupled with a work experience, coupled with a class exercise, coupled with something else. For me…, it was Richard Skalak (period). Early on in my time with him, he and Professor Shu Chien were editors for the Handbook of Bioengineering to be published by McGraw-Hill. This book was to have over 40 chapters written by the greats of the field in bioengineering. In fact, many of the authors were, or went on to be, Lissner Medal honorees. This job required me to read each chapter's draft and proofread for consistency or clarity. Then, I was to contact each of these authors with questions related to their figures, layout, or other matters. In summary, they actually PAID ME to learn about the field and be introduced to the greats of the field. This opportunity was nothing short of amazing!

We worked on this project with Professor Shu Chien whom we met many times up at Columbia's Medical School and who was a great partner for this book. I was really honored that they put this acknowledgment to me in the Handbook of Bioengineering Preface “We also acknowledge with thanks, the very competent and thorough assistance of Louis Soslowsky in proofreading and coordinating manuscripts at Columbia University. His help has facilitated the progress of this project greatly.” They also wrote a small note inside on the cover of the version of the book that I have in my office today: “With many thanks and best regards” and “With appreciation and best wishes” and this was very meaningful to me as a simple undergraduate student, coming from such luminaries in the field (Fig. 3).

As I continued on my undergraduate years working for Professor Skalak, I was fortunate to be able to move “out of the office” and into a research project. I published my first full-length paper titled “Theory of filtration of mixed blood suspensions.” Professor Skalak was the first author, Professor Chien was the last author, and I was the second author. This paper presented a theory for flow of suspensions of blood cells and demonstrated that small concentrations of stiff cells dominated the response. Although I enjoyed this work quite a bit and it allowed me to experience the excitement of publishing as an undergraduate, I was not as interested in blood flow for my Ph.D. thesis. At that time, Professor Skalak introduced me to Professor Van C. Mow who had just been recruited to Columbia from Rensselaer Polytechnic Institute in 1986. This is a photo from Dr. Skalak's 70th birthday symposium in San Diego and an opportunity for me to be with them both together (Fig. 4).

My graduate school years were amazing and the environment that Dr. Mow created for all of us was something we did not truly appreciate or recognize at the time, but it was surely nothing short of brilliance. Shown here is a photo of the lab personnel in approximately 1988 (Fig. 5). The papers that I published during my Ph.D. thesis were mostly related to joint mechanics, some stereophotogrammetry with Gerard Ateshian quantifying the shape of the shoulder surfaces as well as joint contact patterns at both the glenohumeral joint and the subacromial space, as well as measuring the mechanical properties of the inferior glenohumeral ligament. This last paper is still my most highly cited today. We had the great fortune to be well integrated with orthopedic surgeon colleagues Evan Flatow, Roger Pollock, and Lou Bigliani. Those years were truly formative for me and these are people that I still speak with today from literally more than 30 years. The group of graduate students we had was truly unbelievable as well, and again, I wish we would have realized at the time how amazing this group was: Farshid Guilak, Kerry Athanasiou, Lori Setton, Gerard Ateshian, Weiyong Gu, Wenbo Zhu, and others. We were very close friends at the time in graduate school and we realized we had something special but not to the extent we realize now.

After my graduate school years in 1991, I was recruited to the University of Michigan by Professor Steve Goldstein. Steve contacted me before I was really beginning to think about faculty jobs and offered me the opportunity to come out and visit. I have to confess that I only went to visit for what I called “interview practice” as I had never lived west of New Jersey to that time and I was not sure that I ever would. Steve Goldstein was very sincere, and I was impressed by the environment he had created and the opportunity that the University would likely afford me. I did accept the faculty position at that time as I was so impressed by the people and the environment (probably the only thing that really matters when looking for a first faculty job). Interestingly, I accepted the position with a start-up package of a handshake from Steve. He explained that he would be supportive of me and would do everything he could to help me be successful. I could have the existing lab staff assist me as I needed and use the equipment that was already in place. There were no dollar amounts and no written multiyear commitment. It was a good firm handshake and a gentlemen's understanding. I trusted Steve, and although I would take that job again in a heartbeat, I would not recommend anyone today to take a job on a handshake; rather, spend time thinking about what you will need, consult peers and mentors, and for certain, get everything in writing. At Michigan, I was introduced to three orthopedic surgeons that I worked closely with, all of whom I still speak with today: Ralph Blasier, Jim Carpenter, and Jed Kuhn. During that time, we embarked on a series of studies in shoulder joint mechanics that represented more than 40 full length papers over the years. These studies included defining changes in ligament properties with rotator cuff tears to finding those factors that stabilized the shoulder joint in different directions, as well as measuring strain fields in the glenohumeral capsule under different loading conditions. Another series of papers that I began at that time were elucidating structure-function relationships in tendon and I published over 50 papers in this space over the years. I should mention that many of these paper topics overlap, with some of the structure-function relationship papers, for example, related to the shoulder. We began classic structure-function studies in a controlled tendon fascicle model, considering the role of glycosaminoglycans and their chain lengths in structure-function. We developed and used an optical strain system building on the previous systems popularized by Dr. Savio Woo for our field. At this time, I began the use of transgenic mouse models, starting with the Mov13 mouse and moving on to the decorin knockout mouse and then several others. I believe that these might have been the earliest use of a transgenic or knockout model in the tendon field. We then began studies in the rat rotator cuff and published more than 100 papers to date using the rat rotator cuff models. We submitted our first Orthopaedic Research Society abstract on the rat rotator cuff model in 1993 (25 years ago!), presented it at the annual meeting in 1994, and published our first full-length paper with this model in 1996. In that first paper, we evaluated more than 30 animal species as possible models for rotator cuff studies. We considered a variety of important features and factors including anatomic and functional capabilities, and studied the role of overuse and creation of tendinopathy. We evaluated healing of rotator cuff tendons and the role of fibrin clot and a variety of other studies that I will describe as I continue the progression of my career. My time at the University of Michigan was outstanding and I was very happy where I was. Professionally, my research program was flourishing, I had just received my second NIH R01 grant, and I received a promotion to Associate Professor with tenure, just before I left.

It was at that time, in 1997, that I was contacted by Dr. Joseph Iannotti who asked me if I would be interested in a move to the University of Pennsylvania. I was not really sure what he initially meant by that, but it soon became clear. He and others invited me to visit the University and meet with various faculty. It became quickly clear that this was a recruitment visit. In short, I visited again, and in June 1997, I accepted a position at the University of Pennsylvania to begin that November. I was to be the Director of Orthopaedic Research and the Director of the McKay Orthopaedic Research Laboratory. In the 1980s, under the direction of Dr. Carl Brighton, these labs and the orthopedic department were the #1 ranked orthopedic program in the country in terms of funding from the National Institutes of Health. When Dr. Brighton became emeritus in the early 1990s, the program declined steadily to a shell of its former self. In 1995, Dr. Robert Fitzgerald was recruited to be the new Chair of Orthopaedics, and in 1997, I became the Director of Orthopedic Research with the charge to grow back the program. It was there that I met several shoulder surgeons, again with whom I still speak today: Joe Iannotti, Jerry Williams, David Glaser, and my closest orthopedic surgeon collaborator today, Andy Kuntz. We continued our rat rotator cuff studies investigating the role of overuse and exercise, expanded our work not only in tendon but also to muscle. We developed a series of studies evaluating tendon to bone attachment injury and repair, and the role of postoperative immobilization and exercise and how that would affect tendon to bone healing. We developed chronic and delayed repair models, considered the effect that rotator cuff tears had on the long head of the biceps, as well as on articular cartilage. We considered joint damage with cuff tears more broadly, including the balance of forces at the joint, as well as scapular dyskinesis. We continued a series of studies on shoulder mechanics while those animal model studies were ongoing and these studies included tendon strain measures using MRI, strain and tear interactions, and tear progressions, as well as studies with fiber alignment or realignment during joint loading. It was at that time we developed a new line of research looking at neonatal tendon. Looking back, when I started our rat rotator cuff studies, people thought that it would be very difficult as the rat was very small (I heard this concern/critique from many). From that, we went to the smaller mouse models and to even smaller neonatal mouse studies which indeed are really quite small! We defined neonatal tendon properties for the Achilles and the supraspinatus tendons. We studied neonatal Achilles healing and used this as a paradigm for parallels between neonatal development and the healing process. We evaluated crimp behavior and fiber realignment during mechanical testing and these studies considering crimp and fiber realignment went back to the more fundamental structure–function studies where we considered the role of the tissue structure and its mechanical behavior. We published a series of studies following these studying hypercholesterolemia both diet-induced and knock out. We showed that high cholesterol adversely affected not only native tendon properties but tendon repair response to injury as well. Further, we studied tendons across multiple species and looked at parallels there. We determined that treatment with statins can alter tendon properties and we filed and successfully received a couple of patents in that space that was kind of interesting and fun, though a lot of work to get to that point and it was not something we really followed up at that time. We have continued the line of transgenic and knockout mouse models and have published more than 40 papers on this work to date. The first ones were our adult mouse patella tendon models where we determined the role of pro- and anti-inflammatory cytokines IL6 and IL4. After that, we developed and continued multiple studies determining the regulatory role of decorin and biglycan, the most common proteoglycans, in tendon. We studied the effect of aging, fibril structure, and the role of the repair response to injury. We also had and continue to perform a series of studies evaluating Collagen V, including studies on classic Ehler's Danlos syndrome (the heterozygote Collagen V mouse is a model for this disease). Again, we studied the role in development as well as in dynamic response at multiple hierarchical scales. These studies have been and continue to be in collaboration with Professor David Birk who at the time was at Thomas Jefferson University in Philadelphia. He subsequently moved and is presently at the University of South Florida in Tampa. He and I have a very strong collaboration and we publish together regularly. He is actually the single person with whom I have published the greatest number of papers at the present time. He is a developmental biologist with whom I have multiple NIH R01 grants as multi PI's. He serves on many of my students' thesis committees and he has been a great friend and collaborator over the years.

Almost 8 years ago now, I tore my Achilles tendon playing volleyball. After spending considerable time and effort in physical therapy and rehabilitation, I was a bit embarrassed for our field about the state of Achilles tendon postoperative rehabilitation protocols. So…, I wrote an NIH R01 grant in this area of Achilles tendon postoperative activity level and I still have active NIH and other funding in this space! We determined a variety of factors such as that Achilles properties remain inferior long-term, nonsurgical treatment can be as good as surgical treatment, and that fatigue is a very important parameter when measuring mechanics of the Achilles (we found that more quasi-static constant ramp to failure tests showed no difference but when cyclic testing and fatigue were considered, we found dramatic differences across groups and it was an important measure for us). We studied aging demonstrating inferior healing. More recently, we have gotten back to some of the fundamental structure-function experiments determining the role of fibril stretch and fibril sliding, the role of tendon crimp in fatigue loading, and the role of fiber realignment during loading and dynamic processes of structure-function mediators to respond to these processes in the Achilles.

We have also developed a series of in vivo assays over time. Although animal models afford the opportunity to take tissue out for assay that would never be possible in the human condition, it is important to have assays that could mimic the clinical situation for direct translation. We developed a rat gait analysis system which had allowed both kinematic and kinetic measures. These were important as we determined that not only were spatial parameters important but also forces were very important to measure and sometimes they were much more sensitive than spatial parameters to detect differences between treatment groups. We developed methods to measure passive joint stiffness and joint range of motion and we used ultrasound not only to measure cartilage thickness and structure but also for changes in fibril organization, vascularity, and oxygenation throughout healing.

Over the past many years, I have thought about the progression of my career and decided it might be instructive to consider various papers that I have published. Starting around 1990, the first series of my studies shown in blue here represent work in shoulder mechanics, and if you see in each 5 year period, I published seven to ten papers in that area for many years until the present where I really have essentially closed this line of work publishing only one paper in the last few years without a plan to continue in this space going forward (Fig. 6). The rat rotator cuff studies started fairly early in my career shown by the red line and these studies peaked just a couple of years ago publishing 25 papers over a 5 year period, meaning an average of five papers per year. Still today, we publish about four papers per year using the rat rotator cuff model, and even through the next 10 years, I project this will be still a significant component of our lab, maybe publishing approximately three papers a year or so in this space if things continue as expected. During that time, the mouse knockout studies have increased dramatically as shown by the green line. They started a few years later but at the moment represent more than four or five papers published each year by my group. The Achilles studies shown in the purple line started a few years later, but that work is still very active and still on the upswing, publishing a few papers every year. I do think that there will be at least one other topic that will be included in the next phase of my career. I do not know what it is today, but that will result in multiple papers published a year over the next 10 years, if I am right (and lucky)!

As I think about my career in this series of 5 year increments, it is important to note that I try, for the most part, to not just execute a project or two and then “repeat.” Instead, I think about programs I would like to grow and develop, and then embark on fundamental, foundational studies in that programmatic area from which I build. In this way, I have been able to build sustainable long-term funding for my program(s) as they have progressed. For those junior individuals thinking about their own career, do not think because you start in one area, that you have to spend your whole career in that area. I see my career as a series of interconnected areas that have been productive, impactful, and most importantly, fun. We are doing things that I certainly did not even think of during my graduate school years and I would be surprised if I had. For example, I did not touch a single animal (alive or dead) during my graduate work, but my work quickly did utilize multiple animal model systems when I began my faculty career. Allowing research to take you where it does, where things are exciting, and where you have strong collaborators and new opportunities is what keeps things interesting and fun. As I looked back at my publication history for this presentation, I realize that I have more than 25 people with whom I have had more than ten joint publications. This means that there are many people out there with whom I worked closely for a sustained period, represented at least by this metric. I find that very gratifying.

At this point, I would like to recognize and thank all the graduate students I work and have worked with. My graduate students have been the lifeblood of my laboratory and one of the great joys of working in this field. I am particularly proud that 80% of my former Ph.D. students have remained in academics and research and teaching positions although it is by no means something that I require of my students in any way. It just so happened that many of them have been excited by the academic field and continue on. I am also proud that 60% of my former students are women. While I call out my students specifically, I also want to note the postdoctoral trainees, both Ph.D. and MD, medical students, residents, undergraduate students, and others. Additionally, the laboratory staff we have had and continue to have are second to none. They represent a fabulous and committed group who are essential to our team efforts. My laboratory is a multidisciplinary, multifaceted lab. We are very much focused in engineering as that is my background, but we have significant components of biology, imaging, structure, clinical, and other aspects as well. I am very proud of the staff, students, trainees, and colleagues that I have in this lab. I am also proud that we are part of the McKay Orthopedic Research Lab that today has over a hundred twenty five people including about a dozen PI's (Fig. 7). When I started there, it was really was just a few of us at Penn and the Lab has grown dramatically and that has really been quite fabulous. It has been wonderful to be part of this environment as we continue to grow our programs.

Regarding funding sources, a special thank you to the National Institutes of Health (NIH) and, in particular, the National Institute of Arthritis and Musculoskeletal and Skin Disease (NIAMS) is deserved where the very large majority of my research funding has come over the years. I have also had significant funding from the National Science Foundation (NSF) largely through graduate research fellowships for my graduate students. We have been fortunate to receive a number of these over the years and these have been a great source of support for the trainees. We also have funding from the Veterans Administration in the form of Merit and Spire grants. This is another facet to our work that has been great. I have been fortunate to have funding from about ten foundations; historically, the Whitaker Foundation really was my first significant grant at $80,000 a year for 3 years and that was the first extramural grant that launched my career. We are grateful for support from several other foundations such as OREF, AOSSM, ASES, ASSH, AOFAS, and other foundations that have played an important role in my program. I have also had significant funding from industry over the years. I have been supported by almost 20 different companies at one time or another. Some of these are more biotech companies and tissue engineering, some of them are more classic orthopedic companies, and some are new startups. I have had support from industry for three to four different industrial grants concurrently at any one time. Gone are the days when we can support our lab solely on the NIH, solely on the government. It is important to be thoughtful about how you might augment your research portfolio with industrial, foundation, or other grants. We are also pleased to have had some philanthropy to our research program and that has played a truly critical role.

In addition to my “day job” as Professor, I would like to mention some of the other leadership roles I have enjoyed at Penn. I am really proud to serve as Vice Chair for Research in our department. During my time, we have recruited ten new faculty and only one has left in the last 21 years (and that was for an amazing opportunity to be the founding chair of a new biomedical engineering department at another university). All the others remain with us to date and we have continued to grow a really exciting environment. When I came to Penn in 1997, the whole orthopedic department had $500,000 in extramural grant funding. Now, we have grown to over $14 million in research funding. I served as McKay Lab Director for 18 years from 1997 to 2015. Professor Rob Mauck took on that role about 3 years ago and we are really excited because the labs continue to grow. We are looking forward to a major McKay Lab grand reopening for the lab's 40th anniversary in 2019. We moved into our new space at the end of 2018, and at present, have more than 22,000 square feet of continuous space for our programs. In addition to the McKay Lab which is the flagship lab of the orthopedic department, we have had the opportunity to develop many other musculoskeletal research labs primarily based in orthopedics. These include labs at the Veterans Administration, at Children's Hospital, a Human Motion Lab, and several others. We now have a council of musculoskeletal directors that meets on a monthly basis to discuss programmatic opportunities, initiatives, and ways we can interact. I have also been fortunate to be the Founding Director of our Penn Center for Musculoskeletal Disorders. This is a NIH sponsored research center with faculty members from across five Penn school (Medicine, Engineering, Veterinary, Dental, Arts and Sciences) as well from 14 local area institutions. We have opened our doors to many local area institutions that do not have the capabilities or expertise that we have. Three years ago, I took on the role of Associate Dean in our school, presently Associate Dean for Research Integration. My portfolio there includes the oversight of research core facilities across campus, as well as building bridges and programs between the really fabulous Penn schools that are all based on a single campus. I participate broadly on campus in faculty recruiting and a variety of other programs regarding equipment grants, training grants, and other large programmatic initiatives. The opportunity to have new challenges and build programs is something that continues to excite me, in addition to the always exciting research efforts of my lab!

During my time at Penn, I continue to have a large number of close friends and collaborators. I wanted to call out Scott Levin who has been a great partner. He has been our Department of Orthopaedics Chair for the last 9 years and he has been a great supporter of our Orthopaedic Research programs. I also want to call out Rob Mauck who has been on our faculty for more than 13 years. He and I worked together in running our programs; he has been a great partner and friend. I have to say that my move to Philadelphia more than 20 years ago has been great on many levels. By far, the best thing about that move is that this is where I met my wife Judith. When Judith and I got married, we each took on another set of parents and they have been great additions to our family all around. Judith and I have two wonderful kids Rebecca and Daniel both in high school now and I am really proud of the time we get to spend together; it is by far the thing of which I am most proud…, by far (Fig. 8). I want to conclude this presentation by mentioning my primary mentors one more time as without them, none of this would be possible: Richard Skalak for my undergraduate years and the reason I am in the field of bioengineering at all, Van Mow who got me excited about Orthopedic Biomechanics who was a great mentor and taught me a lot about creating great environments, and then Steve Goldstein throughout my junior faculty years. Finally, I would like to thank my parents and my family again who are my true mentors. I learn something from them every day. Thanks again for this wonderful honor.

As I conclude this paper, I was asked to add in some of my thoughts and advice for junior colleagues in the field, so here are a few points to consider. First, it is all about the people and the environment. Surround yourself by people smarter than you, and by people with whom you enjoy interacting, and everything (well almost everything) will be taken care of by itself. I have definitely benefited by my scientific partners and environment. On a related note, keep in mind that none of us are good at everything, so finding opportunities for people where they can excel and enjoy their efforts is essential to building a strong team. Putting those puzzle pieces together to form the best team can be highly rewarding and can result in a strong team. Further, as you are building your team, do not forget that everyone at every level needs a mentor (or two or three or more). Do not feel shy about asking for mentorship (many senior people actually enjoy mentoring, so you are doing them a favor by asking for it!) or by helping others find appropriate mentors. This is essential to succeed throughout a career (and life). Second, as you build out the direction(s) for your lab, always think about the initial things that you need to do to build long-lasting programs, rather than just to complete a series of projects (I described this topic in more detail earlier in this paper). Third, remember that any model you develop or use is…, well…, just a model. Whether it is a computational model, tissue culture model, animal model, or otherwise, always be aware of the strengths and limitations of your system as you set out to answer questions. There is no perfect model (we would not call it a model in that case—it would be the actual thing). Understanding when models have the essential (not all of course) characteristics of what you are trying to model is critical. Fourth, recall that in the end, in many medical disciplines such as orthopedics (the area in which I work), the mechanics is what ultimately matters. How strong is it? Can this potential treatment improve the strength of my repair? How does this tissue respond to load? These are clinically often the most important questions. While biology can often help to answer the how or why which is also important, it is biomechanics that is the most essential component of our studies. Help me remind others that this is, and will continue to be, a simple fact of which we should be proud. Fifth, develop a strategic plan not only for your lab but also for yourself. Where do you want your lab to be in 5 years? Answering what impactful questions? Where do you want to be (not just physically, but professionally and personally) in 5 years? It often takes that long to lay the foundations for those goals, so it is never too early to start. Finally, at least for me, family is by far the most important thing. There is no substitute for a great family and it is important to always try to keep your professional and personal goals in perspective and in balance. It is never easy, but the rewarding things never are. Enjoy our great field!