Four Cornell faculty members from three different colleges received the 2022 Kappa Delta Ann Doner Vaughn Award for their collaborative research on the mechanics and composition of articular cartilage and its relevance to disease.
The award, which recognizes research in musculoskeletal disease or injury with great potential to advance patient care, was presented to Lawrence Bonassar, the Daljit S. and Elaine Sarkaria Professor in the Meinig School of Biomedical Engineering and the Sibley School of Mechanical and Aerospace Engineering at Cornell; Itai Cohen, professor of physics in the College of Arts & Sciences; Lisa Fortier, Ph.D.’98, the James Law Professor of Surgery at the College of Veterinary Medicine; and Michelle Delco ’98, D.V.M.’02, Ph.D.’16, the Harry M. Zweig Assistant Research Professor of Equine Health in the Department of Clinical Sciences at the College of Veterinary Medicine.
The Academy of Orthopaedic Surgeons announced the award Jan. 31, noting “these discoveries by Dr. Bonassar and his colleagues will not only aid in disease prevention and identifying therapeutic windows for treatment, but will play a crucial role in determining the key components and structures in diseased tissues to be targeted for tissue preservation, repair or regeneration.”
For many types of arthritis, such as osteoarthritis, damage begins at the articular cartilage, a very thin surface which covers the ends of bones. Injury and inflammatory mediators induce the release of enzymes, resulting in degradation of the extracellular collagen and aggrecan networks, two of the most important constituents responsible for the mechanical properties of cartilage. Aggrecan is the major proteoglycan in articular cartilage, providing the hydrated gel structure that allows the cartilage to bear loads and dissipate energy.
“A striking feature of connective tissues, such as articular cartilage, is their heterogeneity of composition and structure at multiple length scales,” said Bonassar. “Given the importance of this region, remarkably little is known about the unique mechanical function and biological role in cartilage health and disease. Our research started with a very basic understanding of how cartilage behaves.”
Award recognizes radical collaborators
While Cohen had been studying the behaviors of soft materials, he had not thought about researching cartilage until he partnered with Bonassar more than 15 years ago. The researchers created a testing device that was small enough to fit on a microscope and could capture images at 10-100 milliseconds to observe how the tissue deforms. They discovered that the top 100 microns of articular cartilage has extremely different mechanical behavior than the rest of the tissue. In fact, it was 10-100 times more likely to be deformed.
Their research continued to focus on the biologic implications or cellular responses of tissue with mechanical injury. Bonassar and Cohen partnered with Fortier and Delco, cell biologists and large animal orthopedic surgeons from the College of Veterinary Medicine. This partnership allowed the team to integrate a clinical perspective, as many drivers of arthritis are similar in humans and animals.
Fortier and Delco were interested in therapies that target mitochondria to help prevent damage, and the team demonstrated that delivering a small peptide to the cartilage stabilized the mitochondria and prevented damage to the cells and tissue. The team is currently looking at these peptides as a potential therapeutic for post-traumatic osteoarthritis.
Collectively, the group’s studies have had major impacts on the cartilage and soft tissue biomechanics communities.
“Receiving the Kappa Delta Award is incredibly humbling for me and it’s very meaningful for our team to be recognized,” said Bonassar, who accepted the award on behalf of the Cornell group. “Our interdisciplinary team consisting of an engineer, a physicist and two veterinarians allowed us to look at problems differently from the rest of the field to drive innovation in the clinical setting.”
In its 75-year history, the American Academy of Orthopaedic Surgeons has given more than 110 Kappa Delta Awards. Only 15 of those awards were given to engineers, only three to veterinarians, and none to physicists, according to Bonassar, “demonstrating that the Cornell team is not only pushing forward the boundaries of science, but changing the idea of how scientists work together,” he said.
New research details structural origins of cartilage shear mechanics
On the heels of the Kappa Delta Ann Doner Vaughn Award, Bonassar, Cohen and Fortier co-authored a new study providing key insights on why cartilage mechanically fails.
The study, “Structural origins of cartilage shear mechanics,” was published Feb. 11 in Science Advances and presents a framework that describes the structural origins of cartilage’s shear properties and how they arise from the mechanical interdependence of the collagen and aggrecan networks making up its extracellular matrix.
How cartilage composition determines its mechanical behavior in shear – a major mode of failure – has remained poorly understood by the scientific community, said Thomas Wyse Jackson, doctoral student in the Cohen Group and lead author of the study.
“This framework provides a new quantitative understanding for how the known degradative events in osteoarthritis determine the mechanical changes that are a hallmark of this disease,” Wyse Jackson said. “As such, this work provides a road map for understanding disease progression and in combination with non-invasive techniques, such as MRI, will enable more effective diagnosis and treatment.”
Among the study’s findings is that near the tissue surface, the fibrous collagen network is perilously close to a mechanical phase transition, below which it would not be able to support any shear loads. In this region, the aggrecan reinforces the collagen network and drastically alters the amount of shear load the composite network can handle. Since aggrecan can be synthesized more rapidly than collagen, it can be used to rapidly adjust the tissue stiffness. Collectively these processes allow for generating a hundredfold change in the mechanical shear properties of the tissue while keeping the concentration of collagen nearly constant.
The research was supported by the National Science Foundation and the National Institute of Arthritis and Musculoskeletal and Skin Diseases.