ABSTRACT
OBJECTIVE: The ability of menisci to prevent osteoarthritis (OA) is dependent on the integrity of the complex meniscal entheses, the attachments of the menisci to the underlying subchondral bone (SB). The goal of this study was to determine mechanical and structural changes in meniscal entheses after the onset of OA. DESIGN: Healthy and osteoarthritic meniscal entheses were evaluated for changes in histomorphological characteristics, mineralization, and mechanical properties. Glycosaminoglycans (GAG) and calcium in the insertion were evaluated with histological staining techniques. The extent of calcium deposition was assessed and tidemark (TM) integrity was quantified. Changes in the mineralized zone of the insertion were examined using micro-computed tomography (µCT) to determine bone mineral density, cortical zone thickness, and mineralization gradient. Mechanical properties of the entheses were measured using nano-indentation techniques to obtain material properties based on viscoelastic analysis. RESULTS: GAG thickness in the calcified fibrocartilage (CFC) zone and calcium content were significantly greater in osteoarthritic anterior meniscal entheses. TM integrity was significantly decreased in OA tissue, particularly in the medial anterior (MA) enthesis. The mineralized zone of osteoarthritic meniscal entheses was significantly thicker than in healthy entheses and showed decreased bone mineral density. Fitting of mineralization data to a sigmoidal Gompertz function revealed a lower rate of increase in mineralization in osteoarthritic tissue. Analysis of viscoelastic mechanical properties revealed increased compliance in osteoarthritic tissue. CONCLUSIONS: These data suggest that significant changes occur at meniscal enthesis sites with the onset of OA. Mechanical and structural changes in meniscal entheses may contribute to meniscal extrusion, which has been shown to increase the progression of OA.
Subject(s)
Menisci, Tibial/pathology , Osteoarthritis, Knee/pathology , Adult , Biomechanical Phenomena , Bone Density/physiology , Calcium/analysis , Elastic Modulus , Glycosaminoglycans/analysis , Humans , Menisci, Tibial/diagnostic imaging , Menisci, Tibial/physiopathology , Middle Aged , Osteoarthritis, Knee/diagnostic imaging , Osteoarthritis, Knee/physiopathology , Viscosity , X-Ray MicrotomographyABSTRACT
While much work has previously been done in the modeling of skeletal muscle, no model has, to date, been developed that describes the mechanical behavior with an explicit strain-energy function associated with the active response of skeletal muscle tissue. A model is presented herein that has been developed to accommodate this design consideration using a robust dynamical approach. The model shows excellent agreement with a previously published model of both the active and passive length-tension properties of skeletal muscle.
Subject(s)
Energy Transfer/physiology , Models, Biological , Muscle, Skeletal/physiology , Animals , Anisotropy , Computer Simulation , Elastic Modulus/physiology , Humans , Stress, MechanicalABSTRACT
Motivated by our interest in examining meniscal mechanotransduction processes, we report on the validation of a new tissue engineering bioreactor. This paper describes the design and performance capabilities of a tissue engineering bioreactor for cyclic compression of meniscal explants. We showed that the system maintains a tissue culture environment equivalent to that provided by conventional incubators and that its strain output was uniform and reproducible. The system incorporates a linear actuator and load cell aligned together in a frame that is contained within an incubator and allows for large loads and small displacements. A plunger with six Teflon-filled Delrin compression rods is attached to the actuator compressing up to six tissue explants simultaneously and with even pressure. The bioreactor system was used to study proteoglycan (PG) breakdown in porcine meniscal explants following various input loading tests (0-20% strain, 0-0.1 MPa). The greatest PG breakdown was measured following 20% compressive strain. These strain and stress levels have been shown to correspond to partial meniscectomy. Thus, these data suggest that removing 30-60% of meniscal tissue will result in the breakdown of meniscal tissue proteoglycans.
Subject(s)
Bioreactors , Mechanotransduction, Cellular/physiology , Menisci, Tibial/physiology , Proteoglycans/metabolism , Tissue Culture Techniques/instrumentation , Weight-Bearing/physiology , Animals , Compressive Strength , Equipment Design , Stress, Mechanical , SwineABSTRACT
Fluid flow has been shown to be a potent physical stimulus in the regulation of bone cell metabolism. In addition to membrane shear stress, loading-induced fluid flow will enhance chemotransport due to convection or mass transport thereby affecting the biochemical environment surrounding the cell. This study investigated the role of oscillating fluid flow induced shear stress and chemotransport in cellular mechanotransduction mechanisms in bone. Intracellular calcium mobilization and prostaglandin E(2) (PGE(2)) production were studied with varying levels of shear stress and chemotransport. In this study MC3T3-E1 cells responded to oscillating fluid flow with both an increase in intracellular calcium concentration ([Ca(2+)](i)) and an increase in PGE(2) production. These fluid flow induced responses were modulated by chemotransport. The percentage of cells responding with an [Ca(2+)](i) oscillation increased with increasing flow rate, as did the production of PGE(2). In addition, depriving the cells of nutrients during fluid flow resulted in an inhibition of both [Ca(2+)](i) mobilization and PGE(2) production. These data suggest that depriving the cells of a yet to be determined biochemical factor in media affects the responsiveness of bone cells even at a constant peak shear stress. Chemotransport alone will not elicit a response, but it appears that sufficient nutrient supply or waste removal is needed for the response to oscillating fluid flow induced shear stress.