Magnetic Capture of Osteoarthritis Biomarkers

10/31/2016 - 3:00pm
Kyle D. Allen, Ph.D., Assistant Professor & Associate Chair for Undergraduate Studies, Department of Biomedical Engineering, University of Florida
Communicore, C1-15


Dr. Allen has been working with rodent models of orthopedic diseases for since 2006 and in orthopedic research since 2002.  During his doctoral work with Dr. Kyriacos Athanasiou at Rice University, Dr. Allen characterized the mechanics of the temporomandibular joint (TMJ) disc and refined tissue engineering strategies toward the goal of creating a biological surrogate for degenerating TMJ disc.  During his post-doctoral work with Dr. Lori A. Setton at Duke University, Dr. Allen developed new techniques to analyze rodent gait using high-speed videography and highly sensitive force plates.  These techniques are among the most sensitive analyses available for the detection of rodent gait compensations in preclinical models of musculoskeletal disease and are available to the research community at large through our resources page.  In the Fall 2010, Dr. Allen received a Pathways to Independence Award from NIAMS, and during the K99 Phase of this award, he was co-mentored by Dr. Lori Setton and Dr. Virginia Byers Kraus while investigating the relationships between pain-related behaviors and molecular biomarkers of joint degeneration. This experience remains the centering question for the Orthopaedic Biomedical Engineering Laboratory - how does joint degeneration ultimately result in chronic pain and disability and can we predict these symptoms before they occur?  In the Fall 2011, Dr. Allen started a new laboratory at the University of Florida in the J. Crayton Pruitt Family Department of Biomedical Engineering, where his laboratory continues to develop new techniques that will lead to a better diagnosis and treatment of joint diseases.


Osteoarthritis (OA) involves the slow, chronic degradation of articular joints.  During the degenerative cascade of OA, molecular biomarkers are generated in the OA-affected joint, including cartilage degradation products, catabolic enzymes, inflammatory mediators, chemokines, and other molecules.  These molecules could serve as molecular biomarkers of the OA state and severity; moreover, these diagnostic targets could provide parallel measures across OA translational models – from rodent to canine to man.  In human and large animal joints, synovial fluid can often be recovered via synovial fluid aspirations; however, evaluation of synovial fluid in rodent pre-clinical models – where drug testing and development often begin – has significant technical challenges. First, the volume of synovial fluid is severely limited, making it nearly impossible to directly collect any amount of fluid. Lavage is frequently used to wash the joint; however, this technique significantly dilutes biomarkers and fails to account for the effects of joint effusion. Finally, mixing saline and synovial fluid is non-trivial, especially within the joint, often leading to mixing errors or the extreme dilution of biomarker.  To address these technological limitations, our group has developed a magnetic nanoparticle-based technology to collect biomarkers from synovial fluid, termed magnetic capture.  Using this technology, biomarkers can be magnetically collected from a rodent knee without the need to remove fluid from the joint.  Moreover, magnetic capture determines total biomarker within the joint, a measure less susceptible to joint effusion.  In this seminar, magnetic capture of a collagen degradation product (CTXII) and the magnetic capture methods of a chemokine (MCP1) will be described for rat models of knee OA, demonstrating magnetic capture as a sensitive technique for the assessment of intra-articular levels of OA biomarkers in rodent preclinical models.

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