Novel animal model for Achilles tendinopathy: Controlled experimental study of serial injections of collagenase in rabbits.

Abstract

Our goal was to develop a novel technique for inducing Achilles tendinopathy in animal models which more accurately represents the progressive histological and biomechanical characteristic of chronic Achilles tendinopathy in humans. In this animal research study, forty-five rabbits were randomly assigned to three groups and given bilateral Achilles injections. Low dose (LD group) (n = 18) underwent a novel technique with three low-dose (0.1mg) injections of collagenase that were separated by two weeks, the high dose group (HD) (n = 18) underwent traditional single high-dose (0.3mg) injections, and the third group were controls (n = 9). Six rabbits were sacrificed from each experimental group (LD and HD) at 10, 12 and 16 weeks. Control animals were sacrificed after 16 weeks. Histological and biomechanical properties were then compared in all three groups. At 10 weeks, Bonar score and tendon cross sectional area was highest in HD group, with impaired biomechanical properties compared to LD group. At 12 weeks, Bonar score was higher in LD group, with similar biomechanical findings when compared to HD group. After 16 weeks, Bonar score was significantly increased for both LD group (11,8±2,28) and HD group (5,6±2,51), when compared to controls (2±0,76). LD group showed more pronounced histological and biomechanical findings, including cross sectional area of the tendon, Young's modulus, yield stress and ultimate tensile strength. In conclusion, Achilles tendinopathy in animal models that were induced by serial injections of low-dose collagenase showed more pronounced histological and biomechanical findings after 16 weeks than traditional techniques, mimicking better the progressive and chronic characteristic of the tendinopathy in humans.

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Published Version (Please cite this version)

10.1371/journal.pone.0192769

Publication Info

de Cesar Netto, Cesar, Alexandre Leme Godoy-Santos, Pedro Augusto Pontin, Renato Jose Mendonça Natalino, Cesar Augusto Martins Pereira, Francisco Diego de Oliveira Lima, Lucas Furtado da Fonseca, Jackson Rucker Staggers, et al. (2018). Novel animal model for Achilles tendinopathy: Controlled experimental study of serial injections of collagenase in rabbits. PloS one, 13(2). p. e0192769. 10.1371/journal.pone.0192769 Retrieved from https://hdl.handle.net/10161/27440.

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de Cesar Netto

Cesar de Cesar Netto

Instructor in the Department of Orthopaedic Surgery

The desire to explore, research, and understand things in great detail has been the driving force throughout my career. This passion drew me to Foot and Ankle, a subspecialty expanding in orthopedic knowledge with many unsolved mysteries. After completing my Medical School, Orthopedic Residency, and Foot and Ankle Fellowship at the renowned University of Sao Paulo, ranked number one in Latin America for several years, and after five years of clinical practice in Brazil, this desire to explore and understand also brought me to the United States. As part of my Ph.D. program with the University of Sao Paulo, I joined as a visiting scientist and research fellow for Dr. Lew Schon at the traditional MedStar Union Memorial Hospital in Baltimore-MD, where I developed an animal model of induced Achilles tendinopathy. 

As a practicing physician in Brazil, I achieved multiple goals in my early career. Academics have been a large component of my practice, allowing me to participate in young physicians' education and challenge my understanding of orthopedic fundamentals. As the elected Chief of Orthopaedic Residents from 2011 to 2013, I presented 245 lectures to orthopedic surgeons and in multidisciplinary conferences. My practice as an orthopedic surgeon in Sao Paulo allowed me to combine the Brazilian enthusiasm for soccer, serving as the team physician and Foot and Ankle advisor for the professional soccer team Sport Club Corinthians Paulista for almost five years.

As a Foot and Ankle surgeon, I constantly sought to confront the unsolved questions in our orthopedic practices. During my Ph.D. studies with the University of Sao Paulo, I aimed to maximize my research experience and clinical exposure. During my time in Maryland, I have engaged in multiple research projects, collaborating with MedStar Union Memorial and Johns Hopkins University to evaluate and clinically implement innovative imaging techniques, including weight-bearing CT, dynamic CT, 3D MRI, and metal artifact reduction sequence (MARS) MRI.

I was also amazed by the American medical system's resources that create opportunities for motivated physicians to excel in clinical work, educational teaching endeavors, and research investigations. While this balance requires dedication and precise time management, I have been fortunate to work with a variety of mentors who demonstrated to me how great it could be to practice in the US. With that in mind, I ended up deciding to pursue the Academic Pathway of the ABOS Certification. I have completed a total of three Orthopedic Foot and Ankle Fellowships in the US. The first was at the University of Alabama at Birmingham (UAB), the second at the Hospital for Special Surgery (HSS) in New York City, and the third and final at MedStar Union Memorial Hospital in Baltimore-MD. It was a long but very pleasant and rewarding pathway that allowed me to grow as a person, as a clinician, and as a surgeon while being fortunate to create lifetime bonds with several mentors. Once I was done with my fellowships, my objective was to combine my unique background with my innovative and instructive training and apply the acquired knowledge as an Academic Assistant Professor at the Department of Orthopedics of the Carver College of Medicine at the University of Iowa.

The almost four years in Iowa City have been a blast! The leadership of the Orthopedic Department entirely and constantly supported me, and together, we achieved a lot in a relatively short amount of time. I utilized my academic start-up grant to acquire the first Weight-Bearing CT scanner in the Country that allows the hip, knee, foot, and ankle to be scanned under load simultaneously. With the scanner, I founded and served as the Director of the University of Iowa Orthopedic Functional Imaging Research Laboratory (OFIRL), which rapidly achieved an established, recognized position in the research and orthopedic foot and ankle community. I also had the unique opportunity to care for the State of Iowa community suffering from orthopedic foot and ankle problems, always excelling in providing high-quality and passionate clinical and surgical care. I’ll be forever grateful to my leadership, partners, and colleagues in Iowa City, as well as my patients, who gave me the utmost opportunity to care for them.

As an Associate Professor in the Department of Orthopedics at Duke University, I hope to contribute further to the American society and North Carolina Community, taking excellent care of patients, teaching and mentoring medical students, residents, and fellows, and helping the orthopedic foot and ankle surgery research to excel.


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