Biobased Elastomer Nanofibers Guide Light-Controlled Human-iPSC-Derived Skeletal Myofibers

Aimee Cheesbrough, Fabiola Sciscione, Federica Riccio, Peter Harley, Lea R'Bibo, Georgios Ziakas, Arnold Darbyshire, Ivo Lieberam, Wenhui Song*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

Generating skeletal muscle tissue that mimics the cellular alignment, maturation, and function of native skeletal muscle is an ongoing challenge in disease modeling 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, the synthesis and characterization of a new biobased nanohybrid elastomer, which is electrospun into aligned nanofiber sheets to mimic the skeletal muscle extracellular matrix, is presented. The polymer exhibits remarkable hyperelasticity well-matched to that of native skeletal muscle (≈11–50 kPa), with ultimate strain ≈1000%, and elastic modulus ≈25 kPa. Uniaxially aligned nanofibers guide myoblast alignment, enhance sarcomere formation, and 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 ≈35 W m−3. This system is a promising new skeletal muscle tissue model for applications in muscular disease modeling, drug discovery, and muscle regeneration.

Original languageEnglish
Article number2110441
JournalAdvanced Materials
Volume34
Issue number18
Early online date31 Mar 2022
DOIs
Publication statusPublished - 5 May 2022

Keywords

  • biobased elastomer nanofibers
  • electrospinning
  • human induced pluripotent stem cells
  • myogenic differentiation
  • optogenetics

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