In vitro investigation and biomechanical modeling of the effects of PLF-68 on osteoarthritis in a three-dimensional model |
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Authors: | Kavas Ayşegül Ozdemir Mustafa Gürses Senih Keskin Dilek Tezcaner Ayşen |
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Affiliation: | (1) Department of Chemical Engineering, Faculty of Technology and Metallurgy, University of Belgrade, Karnegijeva 4, 11120 Belgrade, Serbia;(2) Institute of Biomaterials and Biomedical Engineering, University of Toronto, 164 College St, Toronto, Ontario, M5S3G9, Canada;(3) Department of Biomedical Engineering, Columbia University, 363G Engineering Terrace, Mail Code 8904, 1210 Amsterdam Avenue, New York, NY 10027, USA |
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Abstract: | In this study, it was hypothesized that Pluronic F-68 (PLF-68) increases matrix synthesis of osteoarthritis (OA) chondrocytes in addition to its well-documented cell survival effect. To test this hypothesis, rat articular chondrocytes were embedded in agarose discs and were exposed to 5-azacytidine (Aza-C) to induce OA-like alterations. Chondrocytes were then treated with PLF-68 (8 and 12 mg/ml) for 10 days. Aza-C-exposed and PLF-68-untreated chondrocytes and Aza-C-unexposed and PLF-68-untreated chondrocytes were used as negative and positive control groups, respectively. Dynamic hydrostatic pressure (max 0.2 MPa, 0.1 Hz) was applied to discs for 30 min/day (5 days/week). Cell viability, collagen and proteoglycan deposition in discs were determined. Unconfined compression stress relaxation tests were performed to determine peak stress and material parameters of discs—namely spring constants (k 1 and k 2), damping coefficient (η), instantaneous modulus (E 0) and relaxed modulus (E ∞) using Kelvin model to evaluate the functional coherence of the matrix. PLF-68 treatment significantly increased the collagen deposition in discs and viability of OA-like chondrocytes. A dose-dependent increase was also observed for elastic stiffness parameters (k 1, k 2, E 0 and E ∞). Same positive effect of PLF-68 was not observed for proteoglycan deposition. However, dose-dependent increase in η suggests that PLF-68 treatment resulted with the deposition of functional matrix. This is the first study which reports that PLF-68 has also positive effect on collagen synthesis of OA cells. As a conclusion, our results suggest that PLF-68 has a potential for recovery from OA-like alterations, which should be further analyzed. |
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