Organized by: ORS and American Association of Hip and Knee Surgeons (AAHKS)
Moderators: William Mihalko, MD, PhD and Jay Parvizi, MD
This symposium will discuss issues in knee and hip reconstructive surgery from the point of view of the surgeons at the bedside and what they feel needs to be provided by the researchers at the benchside. (The symposium will cover needed solutions to clinical topics including: The forgotten knee replacement, bearing surfaces in total joint replacement, eliminating the periprosthetic joint infection and artificial intelligence in orthopaedics.) The expert faculty will entertain a panel discussion with audience input after presentation of the topics to spark debate on the need for future research.
The Forgotten Total Knee Replacement: Is it Possible?
Brett Levine, MD, Rush University Medical Center
Bearing Surface in Total Joint Replacement: Have We Solved the Problem?
Jesse Otero, MD, PhD, OrthoCarolina Hip and Knee Center
Eliminating PJI: A Dream or Reality?
Matthew Dietz, MD, West Virginia University
Artificial Intelligence in Orthopedics: Let the Game Begin
Ran Schwarzkopf, MD, NYU Langone Orthopedic Hospital
Organizers: Nicola Baldini, MD and Gabriela Graziani, PhD
Preclinical tests are being increasingly recognized as poorly predictive of the clinical outcome of drugs and biomaterials in regenerative medicine, trauma and oncology. New advances in 3D in vitro models of healthy and pathological tissues (bone, tendons, cartilage, intervertebral disc, bone tumors) offer new perspectives for cell-based drugs/biomaterials screening, cell therapy and the study of orthopaedic pathologies. The symposium is dedicated to these new techniques, with a strong focus on 3D printing and bioprinting, microfluidics and live imaging, their clinical perspectives, and the challenges to be met to move towards a personalized, patient specific screening. The topic is discussed from basic scientists’ and clinical scientists’ perspectives. The symposium is endorsed by the EORS- European Orthopaedic Research Society.
3D Models in Intervertebral Disc Regeneration Research
Gianluca Vadalà, MD, PhD, University of Rome
3D Models for Healthy and Aged/Degenerated Tendon Derived Cells
Denitsa Docheva, PhD, University Hospital Regensburg
Biomimetic Models of Bone by Combination of 3D Printing, 3D Bioprinting and Nanostructured Materials
Gabriela Graziani, PhD, Rizzoli Orthopaedic Institute
Moderators: Kathleen Derwin, PhD and Spencer E Szczesny, PhD
Cutting edge integrated sessions incorporating expert panel-defined clinical challenges with clinical and basic researchers presenting biologic underpinnings and translational approaches to treatments on the horizon.
Clinical Presentation of Challenges in the Treatment of Tendinopathy – Bedside to Bench
Scott Rodeo, MD, Hospital for Special Surgery
Connecting Developmental Biology to Tendinopathy Pathogenesis
Alice Huang PhD, Icahn School of Medicine at Mount Sinai
Tissue Specific Stem Cells – Both the Cause and Cure of Disease
Nat Dyment PhD, University of Pennsylvania
Bench to Bedside: How Close Are We to Translational Therapeutics in Tendinopathy?
Neal Millar, MD, PhD, University of Glasgow
Cellular Senescence as a Driver of Osteoarthritis: The Roles of Aging, Obesity and the Immune System
Organized by Brian Johnstone, PhD, and Farshid Guilak, PhD, for the ICORS College of Fellows of International Orthopaedic Research (FIOR)
This symposium will provide evidence that senescence is a key mechanism for communication between various organ systems, and that this is a common pathway for various forms of osteoarthritis. This concept provides a biological basis for the recently advanced view that osteoarthritis is a ‘whole body disease’, not just a ‘whole joint disease’. The latter definition has served the field well, allowing its expansion beyond the originally cartilage-centric focus, but the updated definition drives new therapies, which will be discussed by the panel of speakers.
Osteoarthritis as a Whole Body Disease
Brian Johnstone, PhD, FIOR, FORS
Chondrocyte Senescence During Physiological Aging
Brian Diekman, PhD
Young Patients, Old Joints – Obesity as a Driver of Premature Senescence
Farshid Guilak, PhD, FIOR, FORS
What is a Senescent Cell and What is the Connection to the Immune System?
Jennifer Elisseeff, PhD
Organizers: Bingyun Li, PhD and Jessica Jennings, PhD
Infections like COVID-19 have changed our life. No treatments are currently available for treating or preventing COVID-19 virus infections. These realities have reminded us the challenges in dealing with all kinds of infections, especially those antibiotic resistant infections, which have been increasing seen in the recent decades. This symposium will present the new challenges and recent advances and breakthroughs in the diagnosis (e.g., high throughput screening), prevention (e.g., vaccine development), and treatment (e.g., use of nanotechnology) of musculoskeletal infections.
Staphylococcus Aureus Invasion of the Osteocyte Lacuno-canalicular Network
Edward Schwarz, PhD, University of Rochester
Preventing Musculoskeletal Infections: The Good, the Bad, and the Ugly
Antonia Chen, MD, MBA, Brigham and Women’s Hospital
Antibacterial Electrochemistry at Metallic Biomaterials: Implant Generated Therapeutics
Jeremy Gilbert, PhD, Clemson University
Intracellular Infection and Nanomedicine
Bingyun Li, PhD, West Virginia University
Tom Andriacchi, PhD, Stanford University
The Next Steps Towards Understanding Musculoskeletal Pathology
Restoration of ambulatory function is one of the primary goals of treating disability associated with musculoskeletal pathology. The present state of the art will be illustrated with examples that highlight the unique understanding that comes from applying the methods of gait and joint mechanics to clinical problems. In considering future developments this presentation will illustrate how the current methods evolved from several historical milestones going back to the work of Borelli (circa 1600). Borelli was among the first to apply mechanical principles to analyze how muscular levers act to move and stabilize skeletal segments. These concepts described by Borelli are still used today and provide a framework to illustrate the potential benefits of introducing new disciplines to understanding the complexity of the musculoskeletal system. Finally, the future of gait and joint mechanics will be discussed using examples to illustrate how integrating biological and structural elements with gait mechanics can enhance our understanding of musculoskeletal pathology.
Key points will include:
- The selection gait variables to address specific clinical questions.
- The efficiency of using basic time-distance measures (walking speed, cadence, and stride length) for addressing fundamental clinical questions.
- The use of external measures (kinematics and kinetics) during gait as mechanical signals (“mechanokines”) that influence biological and structural response
- The unique information that can be gained by integrating gait mechanics with biological and structural markers when assessing musculoskeletal health.
Alan J Grodzinsky, ScD, Massachusetts Institute of Technology
From a historical perspective, clinicians and engineers during the 1960s/70s were motivated by the intractable problem osteoarthritis to compare the mechanical and physicochemical properties of normal vs osteoarthritic cartilages from human and animal joints. At the same time, progress on understanding the biochemical composition of cartilage matrix motivated discoveries of the contribution of specific groups of ECM molecules to tissue-level mechanical properties. The highly charged nature of the large aggregating proteoglycans of cartilage (named ‘aggrecan’ in 1988/89) further motivated studies of the electromechanical contributions to biomechanical stiffness and fluid permeability, incorporated into detailed theoretical models of cartilage’s poroviscoelastic properties. Throughout the decades, advances in instrumentation, including the introduction of atomic force microscopy to cartilage biomechanics, enabled new investigations at the pericellular matrix and cellular scales, and even molecular-scale studies of aggrecan and collagen mechanics.
In parallel, discoveries in molecular cell biology over the past 30+ years enabled the evolution of cartilage mechanobiology. Investigators initially focused on the effects of mechanical forces on the anabolic and catabolic responses of chondrocytes in cartilage explants and hydrogel cultures in vitro to static, dynamic and injurious loading forces, and compared the responses to those in the cartilages of whole joints in animals subjected to loading modalities in vivo. Tremendous progress continues to be made by many labs worldwide, and now incorporates systems biology and big-data approaches to an expanded focus on transcriptomic, genomic, proteomic, glycomic, and metabolomic studies across the molecular, cellular and tissue-level length scales of cartilage. Thus, today’s state-of-the-art knowledge of cartilage biomechanics and mechanobiology is truly multiscale, and continues to be motivated by the biology, engineering, and clinical perspectives of joint disease.
Anne-Marie Malfait, MD, PhD, Rush University
Pain arising as a symptom of osteoarthritis is a formidable problem worldwide. NSAIDs and opioids are widely used, but these drugs generally do not provide sustained pain relief and they have considerable side effects that make their chronic use problematic. Newer approaches in clinical trials, such as the sequestration of the neurotrophin, nerve growth factor (NGF), are promising but are associated with ill-understood side effects such as rapidly progressive osteoarthritis. A better understanding of the molecular and cellular basis of osteoarthritis pain should help to discover new therapeutic targets for analgesic drug development, and further elucidate the relationship between joint damage and pain. This problem can now be tackled by a variety of techniques that bring together the disciplines of arthritis research and neuroscience – for example, the development of clinically relevant behavioral tests for osteoarthritis pain in relevant animal models, single cell transcriptomics designed to elucidate the molecular characteristics of populations of joint nociceptors, genetic techniques that allow the identification of neuronal subsets through the expression of fluorescent markers enabling their anatomical characterization assisted by clearing methods, in vivo calcium imaging and related methods for assessing the physiological functioning of relevant pain pathways in real time, and molecular characterization in human neuronal tissues. New insights from such cross-disciplinary studies are expected to reveal novel mechanism-based, tailored strategies for addressing osteoarthritis.
