Empowering engineered muscle in biohybrid pump by extending connexin 43 duration with reduced graphene oxides

Eunkyung Ko; Onur Aydin; Zhengwei Li; Lauren Gapinske; Kai-Yu Huang; Taher Saif; Rashid Bashir; Hyunjoon Kong

doi:10.1016/j.biomaterials.2022.121643

Empowering engineered muscle in biohybrid pump by extending connexin 43 duration with reduced graphene oxides

Biomaterials. 2022 Aug:287:121643. doi: 10.1016/j.biomaterials.2022.121643. Epub 2022 Jun 24.

Authors

Eunkyung Ko¹, Onur Aydin², Zhengwei Li², Lauren Gapinske³, Kai-Yu Huang⁴, Taher Saif², Rashid Bashir⁵, Hyunjoon Kong⁶

Affiliations

¹ Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Micro and Nanotechnology Laboratory, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
² Department of Mechanical Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
³ Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Micro and Nanotechnology Laboratory, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
⁴ Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
⁵ Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Micro and Nanotechnology Laboratory, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL, USA; Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, USA. Electronic address: rbashir@illinois.edu.
⁶ Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL, USA; Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, USA; Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; KU-KIST Graduate School of Converging Science and Technology, Korea University, Seongbuk-gu, Seoul 02841, South Korea. Electronic address: hjkong06@illinois.edu.

PMID: 35772349
DOI: 10.1016/j.biomaterials.2022.121643

Abstract

Engineered skeletal muscle act as therapeutics invaluable to treat injured or diseased muscle and a "living" material essential to assemble biological machinery. For normal development, skeletal myoblasts should express connexin 43, one of the gap junction proteins that promote myoblast fusion and myogenesis, during the early differentiation stage. However, myoblasts cultured in vitro often down-regulate connexin 43 before differentiation, limiting myogenesis and muscle contraction. This study demonstrates that tethering myoblasts with reduced graphene oxide (rGO) slows connexin 43 regression during early differentiation and increases myogenic mRNA synthesis. The whole RNA sequencing also confirms that the rGO on cells increases regulator genes for myogenesis, including troponin, while decreasing negative regulator genes. The resulting myotubes generated a three-fold larger contraction force than the rGO-free myotubes. Accordingly, a valveless biohybrid pump assembled with the rGO-tethered muscle increased the fluid velocity and flow rate considerably. The results of this study would provide an important foundation for developing physiologically relevant muscle and powering up biomachines that will be used for various bioscience studies and unexplored applications.

Keywords: Biohybrid pump; Connexin 43; Gap junction protein; Reduced graphene oxide; Skeletal muscle; Troponin.