TY - JOUR
T1 - Biobased Elastomer Nanofibers Guide Light-Controlled Human-iPSC-Derived Skeletal Myofibers
AU - Cheesbrough, Aimee
AU - Sciscione, Fabiola
AU - Riccio, Federica
AU - Harley, Peter
AU - R'Bibo, Lea
AU - Ziakas, Georgios
AU - Darbyshire, Arnold
AU - Lieberam, Ivo
AU - Song, Wenhui
N1 - Funding Information:
The authors acknowledge financial support by the Engineering and Physical Science Research Council, the United Kingdom (EPSRC grant nos. EP/L020904/1, EP/M026884/1, and EP/R02961X/1, W.S.), and the Medical Research Council (MR/N025865/1, I.L.). A.C. was supported by a BBSRC LIDo Ph.D. studentship (BB/M009513/1), and F.R. and P.H. by Wellcome Trust ?Cell Therapies & Regenerative Medicine? Ph.D. studentships (108874/Z/15/Z). The authors also acknowledge financial support from the Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy's & St Thomas? NHS Foundation Trust in partnership with King's College London and King's College Hospital NHS Foundation Trust. The authors acknowledge the Medical Research Council Centre grant MR/N026063/1. The authors also thank Dr. Thomas Maltby for the design, fabrication, and installation the custom-built electrospinning set-up, and Jishizhan Chen for assistance with AFM imaging. The authors are also grateful to the Wellcome Trust and MRC for funding through the Human Induced Pluripotent Stem Cell Initiative (WT098503). HipSci Lines samples were collected from consented research volunteer recruited from the NIHR Cambridge BioResource through https://www.cambridgebioresource.group.cam.ac.uk/. Initially, 250 normal samples were collected under ethics for iPSC derivation (REC Ref: 09/H0304/77, V2 04/01/2013), which require managed data access for all genetically identifying data, including genotypes, sequence, and microarray data (?managed access samples?). In parallel the HipSci consortium obtained new ethics approval for a revised consent (REC Ref: 09/H0304/77, V3 15/03/2013), under which all data, except from the Y chromosome from males, can be made openly available (Y chromosome data can be used to de-identify men by surname matching), and samples since October 2013 have been collected with this revised consent (?open access samples?). ToC figure created with Biorender.com.
Funding Information:
The authors acknowledge financial support by the Engineering and Physical Science Research Council, the United Kingdom (EPSRC grant nos. EP/L020904/1, EP/M026884/1, and EP/R02961X/1, W.S.), and the Medical Research Council (MR/N025865/1, I.L.). A.C. was supported by a BBSRC LIDo Ph.D. studentship (BB/M009513/1), and F.R. and P.H. by Wellcome Trust “Cell Therapies & Regenerative Medicine” Ph.D. studentships (108874/Z/15/Z). The authors also acknowledge financial support from the Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy's & St Thomas’ NHS Foundation Trust in partnership with King's College London and King's College Hospital NHS Foundation Trust. The authors acknowledge the Medical Research Council Centre grant MR/N026063/1. The authors also thank Dr. Thomas Maltby for the design, fabrication, and installation the custom‐built electrospinning set‐up, and Jishizhan Chen for assistance with AFM imaging. The authors are also grateful to the Wellcome Trust and MRC for funding through the Human Induced Pluripotent Stem Cell Initiative (WT098503). HipSci Lines samples were collected from consented research volunteer recruited from the NIHR Cambridge BioResource through https://www.cambridgebioresource.group.cam.ac.uk/. Initially, 250 normal samples were collected under ethics for iPSC derivation (REC Ref: 09/H0304/77, V2 04/01/2013), which require managed data access for all genetically identifying data, including genotypes, sequence, and microarray data (“managed access samples”). In parallel the HipSci consortium obtained new ethics approval for a revised consent (REC Ref: 09/H0304/77, V3 15/03/2013), under which all data, except from the Y chromosome from males, can be made openly available (Y chromosome data can be used to de‐identify men by surname matching), and samples since October 2013 have been collected with this revised consent (“open access samples”). ToC figure created with Biorender.com.
Publisher Copyright:
© 2022 The Authors. Advanced Materials published by Wiley-VCH GmbH.
PY - 2022/5/5
Y1 - 2022/5/5
N2 - 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.
AB - 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.
KW - biobased elastomer nanofibers
KW - electrospinning
KW - human induced pluripotent stem cells
KW - myogenic differentiation
KW - optogenetics
UR - http://www.scopus.com/inward/record.url?scp=85127404519&partnerID=8YFLogxK
U2 - 10.1002/adma.202110441
DO - 10.1002/adma.202110441
M3 - Article
AN - SCOPUS:85127404519
SN - 0935-9648
VL - 34
JO - Advanced Materials
JF - Advanced Materials
IS - 18
M1 - 2110441
ER -
