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Decellularised cartilage directs chondrogenic differentiation: creation of a fracture callus mimetic

Vas, WJ; Shah, M; Blacker, TS; Duchen, MR; Sibbons, P; Roberts, SJ; (2018) Decellularised cartilage directs chondrogenic differentiation: creation of a fracture callus mimetic. Tissue engineering Part A 10.1089/ten.TEA.2017.0450. (In press). Green open access

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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.

Type: Article
Title: Decellularised cartilage directs chondrogenic differentiation: creation of a fracture callus mimetic
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1089/ten.TEA.2017.0450
Publisher version: http://dx.doi.org/10.1089/ten.TEA.2017.0450
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Ortho and MSK Science
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Physics and Astronomy
URI: https://discovery.ucl.ac.uk/id/eprint/10046717
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