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Publication Detail
Decellularised cartilage directs chondrogenic differentiation: creation of a fracture callus mimetic.
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Article
  • Authors:
    Vas WJ, Shah M, Blacker TS, Duchen MR, Sibbons P, Roberts SJ
  • Publication date:
    27/03/2018
  • Journal:
    Tissue engineering. Part A
  • Medium:
    Print-Electronic
  • Status:
    Published
  • Print ISSN:
    1937-3341
  • Language:
    eng
  • Addresses:
    University College London Division of Surgery and Interventional Science, 159099, Department of Materials and Tissue, London, Stanmore, United Kingdom of Great Britain and Northern Ireland ; wollis.vas.14@ucl.ac.uk.
Abstract
Complications that arise from impaired fracture healing have considerable socioeconomic implications. Current research in the field of bone tissue engineering predominantly aims to mimic the mature bone tissue microenvironment. This approach, however, may produce implants that are intrinsically unresponsive to the cues present during the initiation of fracture repair. As such, this study describes the development of decellularised xenogeneic hyaline cartilage matrix in an attempt to mimic the initial reparative phase of fracture repair. Three approaches based on vacuum-assisted osmotic shock (Vac-OS), Triton X (Vac-Stx) and SDS (Vac-SDS) were investigated. The Vac-OS methodology reduced DNA content below 50ng/mg of tissue, whilst retaining 85% of the sGAG content and as such was selected as the optimal methodology for decellularisation. The resultant Vac-OS scaffolds (dcECM) were also devoid of the immunogenic alpha-gal epitope. Furthermore, minimal disruption to the structural integrity of the dcECM was demonstrated using differential scanning calorimetry (DSC) and fluorescence lifetime imaging microscopy (FLIM). The biological integrity of the dcECM was confirmed by its ability to drive the chondrogenic commitment and differentiation of human chondrocytes and periosteum-derived cells respectively. Furthermore, histological examination of dcECM constructs implanted in immunocompetent mice revealed a predominantly M2-macrophage driven regenerative response both at 2 and 8 weeks post-implantation. These findings contrasted with the implanted native costal cartilage that elicited a predominantly M1-macrophage mediated inflammatory response. This study highlights the capacity of dcECM from the Vac-OS methodology to direct the key biological processes of endochondral ossification, thus potentially recapitulating the callus phase of fracture repair.
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Dept of Physics & Astronomy
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Cell & Developmental Biology
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Department of Ortho and MSK Science
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Div of Surgery & Interventional Sci
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