Our experiments have uncovered a surprising and novel mechanism of cell death in cartilage following mechanical trauma: membrane rupture due to tensile stresses experienced during the removal of an extreme contact force. Although murine chondrocytes are highly resistant to cell death during application of an extreme compressive force, rapid removal of this force induces reproducible cell death in just a few seconds. We call this process cell lysis after removal of compression (CLARC). Our finite element simulations that account for the “triphasic” material properties of cartilage—i.e., its solid component, its fluid component and an ionic phase—demonstrate that sudden unloading of an injurious force can induce a tensile stress in individual cells that exceeds the critical stress for membrane rupture. Thus, our overall objective in this research is to establish CLARC as an important factor in the development and progression of post-traumatic osteoarthritis and a possible target for preventative care. Our experiments are performed using a custom, microscope mounted device that enables simultaneous live/dead imaging and tracking of local strain in fully intact mouse cartilage subject to controlled compressive stresses.
Learn more about A Novel Mechanism of Trauma-induced Cell Death in Articular Cartilage
In collaboration with Dr. Yousuf Khalifa at Emory University, we are working to characterize the depth- and location-dependent material properties of the cornea in tension, compression and shear by combining simultaneous high-speed microscopy, force measurement and control of deformation on viable corneal explants. By correlating our data with structural and compositional data that can be obtained in vivo, we aim to enable novel clinical tools that can identify focal changes in corneal mechanics and thereby aid in the diagnosis and treatment of keratoconus and other diseases of the cornea. Similar studies are underway in the sclera, where local mechanical changes that alter the shape--and, in turn, the optics--of the pressurized eye could be key factors in the onset and progression of myopia.
Learn more about Biomechanics of the Cornea and Sclera
Insertional Achilles tendinopathy (IAT) is a common and debilitating condition that is challenging to treat clinically. Non-surgical interventions for this disease have been largely ineffective with approximately 50% of IAT patients failing conservative care and undergoing surgery. To improve clinical outcomes for IAT patients, there is a need to develop new standards for treatment of this disease.
Learn more about In vivo and In vitro Assessment of Non-operative Therapies for Insertional Achilles Tendinopathy
In-vivo studies of horse flexor tendons and human Achilles tendons have measured temperatures greater than 45⁰ C and 41⁰ C (respectively) during activity as a result of viscoelastic dissipation. Since these high temperatures could impact cell activity and potentially induce cell necrosis, it has been speculated that intra-tendinous viscoelastic hyperthermia could play a key role in tendon pathology. Nevertheless, while the viscoelastic properties of tendon are known to vary substantially with anatomical location and age, the regionally-varying temperatures generated in multiple tendons tested in different stages of life are unknown.
Learn more about Investigating Viscoelastic Hyperthermia in Multiple Young and Aging Tendons