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    The effect of synthetic cannabinoids on wound healing of chondrocytes monolayers and pseudo 3D cartilage tissue. Effect of different concentrations of synthetic cannabinoids WIN55, 212-2, URB602 and HU-308 with and without their antagonists on wound healing of chondrocyte monolayers and pseudo 3D cartilage tissue.

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    A.I.A. ABDElDAYEM.pdf (4.676Mb)
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    Publication date
    2014-05-07
    Author
    Abdeldayem, Ali I.A.
    Supervisor
    Youseffi, Mansour
    Denyer, Morgan C.T.
    Keyword
    WIN55
    212-2
    URB602
    HU-308
    AM630
    LY-320
    135
    Wound healing
    Chondrocyte
    Anti-inflammatory agent
    Cartilage repair
    Cannabinoids
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    Rights
    Creative Commons License
    The University of Bradford theses are licenced under a Creative Commons Licence.
    Institution
    University of Bradford
    Department
    Division of Medical Engineering, School of Engineering, Design and Technology
    Awarded
    2013
    
    Metadata
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    Abstract
    Studies have been conducted to highlight the anti-inflammatory and immunosuppressive properties of cannabinoids and also their potentials for cartilage repair and regeneration. Various wound healing techniques can be used to investigate the mechanisms of chondrocyte repair in monolayers or three dimensional tissue constructs. The effect of different concentrations of the synthetic cannabinoids WIN55, 212-2 (WIN-2), URB602 and HU-308 with and without their antagonists on the wound healing of chondrocyte monolayers was investigated using a simple scratch assay model. The three cannabinoids were found to increase wound healing of chondrocyte monolayers, but at different rates. WIN55, 212-2 at a concentration of 1μM had the highest effect of increasing both migration and proliferation of chondrocytes cultured in a chondrogenic media, which increased the rate of wound closure. It was also found that treating the cells with 2μM of any of the cannabinoids lead to a decrease in cell proliferation and the rate of wound closure. These findings were further investigated, by studying the effect of WIN-2 on nitric oxide (NO) and matrix metalloproteinase-2 (MMP-2) expressed by wounded chondrocyte monolayers. Moreover, expression of collagen type-I, collagen type-II, fibronectin and S100 proteins were detected using immunofluorescence and verified quantitatively using ELISA based techniques, following treatment with 1μM and 2μM of WIN-2, for both 2D monolayers and 3D sheets. Treating chondrocytes with 1μM of WIN-2 significantly increased collagen type-II, fibronectin and S100, and significantly reduced collagen type-I compared to control groups in monolayers and chondrocyte cell sheets. On the other hand, both concentrations of WIN-2 significantly reduced the expression of the inflammation markers NO, and MMP-2, in a dose dependent manner. These findings highlight the potential use of the synthetic cannabinoid for improving the rate of wound closure as well as acting as an antiinflammatory agent, which could be used to enhance tissue engineering protocols aimed at cartilage repair.
    URI
    http://hdl.handle.net/10454/6316
    Type
    Thesis
    Qualification name
    PhD
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