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In vitro investigation and biomechanical modeling of the effects of PLF-68 on osteoarthritis in a three-dimensional model

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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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Authors and Affiliations

  1. Department of Engineering Sciences, Middle East Technical University, 06531, Ankara, Turkey

    Ayşegül Kavas, Senih Gürses, Dilek Keskin & Ayşen Tezcaner

  2. Department of Mechanical Engineering, Middle East Technical University, 06531, Ankara, Turkey

    Mustafa Özdemir

  3. Graduate School of Biomedical Engineering, Middle East Technical University, 06531, Ankara, Turkey

    Senih Gürses, Dilek Keskin & Ayşen Tezcaner

Authors
  1. Ayşegül Kavas
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  2. Mustafa Özdemir
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  3. Senih Gürses
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  4. Dilek Keskin
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  5. Ayşen Tezcaner
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Correspondence to Ayşen Tezcaner.

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The poster presentation of the work was performed at the International Symposium on Biotechnology: Developments and Trends, Middle East Technical University, Ankara, Turkey, September 2009.

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Kavas, A., Özdemir, M., Gürses, S. et al. In vitro investigation and biomechanical modeling of the effects of PLF-68 on osteoarthritis in a three-dimensional model. Biomech Model Mechanobiol 10, 641–650 (2011). https://doi.org/10.1007/s10237-010-0262-2

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