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Biobased Elastomer Nanofibers Guide Light‐controlled Human iPSC‐derived Skeletal Myofibers

Cheesbrough, Aimee; Sciscione, Fabiola; Riccio, Federica; Harley, Peter; R'Bibo, Lea; Ziakas, Georgios; Darbyshire, Arnold; ... Song, Wenhui; + view all (2022) Biobased Elastomer Nanofibers Guide Light‐controlled Human iPSC‐derived Skeletal Myofibers. Advanced Materials , Article 2110441. 10.1002/adma.202110441. (In press). Green open access

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Abstract

Generating skeletal muscle tissue which mimics the cellular alignment, maturation and function of native skeletal muscle is an ongoing challenge in disease modelling and regenerative therapies. Skeletal muscle cultures require extracellular guidance and mechanical support to stabilize contractile myofibers. Existing microfabrication-based solutions are limited by complex fabrication steps, low throughput, and challenges in measuring dynamic contractile function. Here we present the synthesis and characterization of a new biobased nanohybrid elastomer which is electrospun into aligned nanofiber sheets to mimic the skeletal muscle extracellular matrix. The polymer exhibits remarkable hyperelasticity well-matched to that of native skeletal muscle (∼11-50 kPa), with ultimate strain ∼1000% and elastic modulus ∼25kPa. Uniaxially aligned nanofibers guide myoblast alignment, enhance sarcomere formation, promote a ∼32% increase in myotube fusion and ∼50% increase in myofiber maturation. The elastomer nanofibers stabilize optogenetically-controlled human induced pluripotent stem cell-derived skeletal myofibers. When activated by blue light, the myofiber-nanofiber hybrid constructs maintain a significantly higher (> 200%) contraction velocity and specific force (> 280%) compared to conventional culture methods. The engineered myofibers exhibit a power density of ∼35W m−3. This system is a promising new skeletal muscle tissue model for applications in muscular disease modelling, drug discovery and muscle regeneration.

Type: Article
Title: Biobased Elastomer Nanofibers Guide Light‐controlled Human iPSC‐derived Skeletal Myofibers
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/adma.202110441
Publisher version: https://doi.org/10.1002/adma.202110441
Language: English
Additional information: Copyright © 2022 The Authors. Advanced Materials published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and repro-duction in any medium, provided the original work is properly cited.
Keywords: biobased elastomer nanofibers, electrospinning, human iPSCs, myogenic differentiation, optogenetics
UCL classification: 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 > Department of Surgical Biotechnology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
URI: https://discovery.ucl.ac.uk/id/eprint/10144521
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