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Development of Tissue Engineered Skeletal Muscle Manufacturing Variables

Wragg, N; Player, D; Martin, N; Liu, Y; Lewis, M; (2019) Development of Tissue Engineered Skeletal Muscle Manufacturing Variables. Biotechnology and Bioengineering , 116 (9) pp. 2364-2376. 10.1002/bit.27074. Green open access

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Abstract

Three‐dimensional (3D) tissue engineered structures enable more representative determination of novel drug or material effects on tissue than traditional monolayer cell cultures. This work sought to better understand how key manufacturing variables affect the myotube characteristics of a skeletal muscle model toward reducing resource use and to develop an understanding of scaling on model consistency. C2C12 murine myoblasts were seeded in a tethered collagen scaffold from which directional myotubes form in response to lines of tension and a change in medium. Collagen polymerising area length‐to‐width ratios greater than one were found to reduced cell‐matrix attachment and remodelling forces significantly (p<0.05) correlating to a reduction in cell‐fusion potential. Following this, utilising a factorial design‐of‐experiment, 4 million C2C12s/mL, with a polymerising area width 150% of the anchor point, produced the most favourable myotube characteristics and dramatically reduced the incidence of rupture. Scaled constructs showed no significant differences when compared to larger models. Approximately 20 myotubes with a variation in alignment of less than 25 degrees in the central region were consistently observed in the final models. This demonstrates the influence of initial manufacturing variables on tissue formation and has produced a benchmark model for consistent production across scaled constructs for future optimisation and as a potential cost‐effective pre‐clinical testbed.

Type: Article
Title: Development of Tissue Engineered Skeletal Muscle Manufacturing Variables
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/bit.27074
Publisher version: https://doi.org/10.1002/bit.27074
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.
Keywords: Biomanufacturing, In Vitro, Scale down, Skeletal Muscle, Tissue Engineering
UCL classification: UCL
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 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
URI: https://discovery.ucl.ac.uk/id/eprint/10074936
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