Tissue engineering of skeletal muscle has been proposed as a potential regenerative treatment for extensive muscle damage. In this regard, the highly organized structure of skeletal muscles makes the alignment of cells especially indispensable in muscle tissue engineering. However, achieving the desired alignment continues to prove challenging, particularly in 3D engineered tissue constructs. In this study, a biomimetic approach for the generation of functional skeletal muscle fascicle-like tissues by recapitulating 3D muscle-like cellular and extracellular organization, is demonstrated. Anisotropic 3D alignment of muscle extracellular matrix (MEM) nanofibrils capable of providing a pro-myogenic microenvironment by regulating the kinetics of fibrillogenesis in a stretchable elastomeric chip, is achieved. Reprogrammed muscle progenitor cells develop myofibers along the aligned MEM nanofibrils in a 3D configuration, culminating in the structural and functional maturation of skeletal muscle. The resultant 3D muscle fascicle-like constructs support de novo muscle regeneration and induce functional restoration of injured muscles in animal models inflicted with volumetric muscle loss and congenital muscular dystrophy. This study not only highlights the fundamental roles of the muscle–mimetic structural guidance cues for 3D muscle tissue engineering, but also unveils the clinical potential of artificial muscle constructs in regenerative medicine.
Bibliographical noteFunding Information:
The animal experimental procedures using volumetric muscle loss (VML) mouse model were approved by the Institutional Animal Care and Use Committee (IACUC) of Yonsei University Health System (permit number: IACUC‐2017‐0162) and the IACUC of Yonsei University (permit number: IACUC‐A‐201612‐534‐03). An experiment using mdx mice was approved by the IACUC of Dankook University (DKU‐18‐042). All animals were provided with food and water ad libitum in alternating 12‐h light/dark cycles and maintained in a temperature‐controlled animal care facility according to the animal protection regulations, and all efforts were made to minimize suffering as well as to regulate the number of animals used. This work was supported by a grant from the National Research Foundation of Korea (NRF) (2017R1A2B3005994) funded by the Ministry of Science and ICT. This work was also supported by a grant (19172MFDS168) funded by the Ministry of Food and Drug Safety (MFDS), and the Institute for Basic Science (IBS‐R026‐D1). Additionally, support was also received from the Brain Research Program through the NRF funded by the Ministry of Science and ICT (NRF‐2018M3C7A1056896) as well as the KIST Institutional Program (KIST Young Fellow; Project no. 2V05920). This work was supported in part by the KU‐KIST Graduate School of Converging Science and Technology Program.
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All Science Journal Classification (ASJC) codes
- Materials Science(all)
- Condensed Matter Physics