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      Effects of solute size and tissue composition on molecular and macromolecular diffusivity in human knee cartilage


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          Articular cartilage is an avascular tissue. Accordingly, diffusivity represents a fundamental transport mechanism for nutrients and other molecular signals regulating its cell metabolism and maintenance of the extracellular matrix. Understanding how solutes spread into articular cartilage is crucial to elucidating its pathologies, and to designing treatments for repair and restoration of its extracellular matrix. As in other connective tissues, diffusivity in articular cartilage may vary depending both its composition and the specific diffusing solute. Hence, this study investigated the roles of solute size and tissue composition on molecular diffusion in knee articular cartilage.


          FRAP tests were conducted to measure diffusivity of five molecular probes, with size ranging from ~332Da to 70,000Da, in human knee articular cartilage. The measured diffusion coefficients were related to molecular size, as well as water and glycosaminoglycan (GAG) content of femoral and tibial condyle cartilage.


          Diffusivity was affected by molecular size, with the magnitude of the diffusion coefficients decreasing as the Stokes radius of the probe increased. The values of diffusion coefficients in tibial and femoral samples were not significantly different from one another, despite the fact that tibial samples exhibited significantly higher water content and lower GAG content of the femoral specimens. Water content did not affect diffusivity. In contrast, diffusivities of large molecules were sensitive to GAG content.


          This study provides new knowledge on the mechanisms of diffusion in articular cartilage. Our findings can be leveraged to further investigate osteoarthritis and to design treatments for cartilage restoration or replacement.

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          Most cited references50

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          Solute Diffusion within Hydrogels. Mechanisms and Models

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            Progress in intra-articular therapy.

            Diarthrodial joints are well suited to intra-articular injection, and the local delivery of therapeutics in this fashion brings several potential advantages to the treatment of a wide range of arthropathies. Possible benefits over systemic delivery include increased bioavailability, reduced systemic exposure, fewer adverse events, and lower total drug costs. Nevertheless, intra-articular therapy is challenging because of the rapid egress of injected materials from the joint space; this elimination is true of both small molecules, which exit via synovial capillaries, and of macromolecules, which are cleared by the lymphatic system. In general, soluble materials have an intra-articular dwell time measured only in hours. Corticosteroids and hyaluronate preparations constitute the mainstay of FDA-approved intra-articular therapeutics. Recombinant proteins, autologous blood products and analgesics have also found clinical use via intra-articular delivery. Several alternative approaches, such as local delivery of cell and gene therapy, as well as the use of microparticles, liposomes, and modified drugs, are in various stages of preclinical development.
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              The impact of osteoarthritis in the United States: a population-health perspective.

              Arthritis, of which osteoarthritis (OA) is the most common type, is the most frequent cause of disability among adults in the United States. The authors reviewed the epidemiologic literature to identify studies that describe the population-based burden of OA-that is, the burden in all adults in the community. They found that 27 million adults-more than 10% of the U.S. adult population-had clinical OA in 2005, and in 2009 OA was the fourth most common cause of hospitalization. OA is the leading indication for joint replacement surgery; 905,000 knee and hip replacements were performed in 2009 at a cost of $42.3 billion. Obesity is a strong risk factor for OA of the knee and hip. Nurses can improve the quality of life of people with OA by raising awareness among their patients and peers of the substantial OA burden and the strategies, such as physical activity, that can reduce it.

                Author and article information

                Osteoarthr Cartil Open
                Osteoarthr Cartil Open
                Osteoarthritis and Cartilage Open
                24 July 2020
                December 2020
                24 July 2020
                : 2
                : 4
                [a ]Department of Mechanical and Aerospace Engineering, University of Miami, Coral Gables, FL, USA
                [b ]Department of Orthopaedic Surgery, University of Miami, Miami, FL, USA
                [c ]Max Biedermann Institute for Biomechanics at Mount Sinai Medical Center, Miami Beach, FL, USA
                [d ]Department of Biomedical Engineering, University of Miami, Coral Gables, FL, USA
                Author notes
                []Corresponding author. College of Engineering, University of Miami, 1251 Memorial Drive, MEB 276, Coral Gables, FL, 33146, USA. f.travascio@ 123456miami.edu
                [∗∗ ]Corresponding author. College of Engineering, University of Miami, 1251 Memorial Drive, MEA 219, Coral Gables, FL, 33146, USA. a.jackson2@ 123456miami.edu
                S2665-9131(20)30078-9 100087
                © 2020 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                ORIGINAL PAPER

                fluorescence recovery after photobleaching (frap),glycosaminoglycan (gag),water content,stokes radius


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