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Efficient myotube formation in 3D bioprinted tissue construct by biochemical and topographical cues
Open accessAbstract
Biochemical and biophysical cues directly affect cell morphology, adhesion, proliferation, and phenotype, as well as differentiation; thus, they have been commonly utilized for designing and developing biomaterial systems for tissue engineering applications. To bioengineer skeletal muscle tissues, the efficient and stable formation of aligned fibrous multinucleated myotubes is essential. To achieve this goal, we employed a decellularized extracellular matrix (dECM) as a biochemical component and a modified three-dimensional (3D) cell-printing process to produce an in situ uniaxially aligned/micro-topographical structure. The dECM was derived from the decellularization of porcine skeletal muscles and chemically modified by methacrylate process to enhance mechanical stability. By using this ECM-based material and the 3D printing capability, we were able to produce a cell-laden dECM-based structure with unique topographical cues. The myoblasts (C2C12 cell line) laden in the printed structure were aligned and differentiated with a high degree of myotube formation, owing to the synergistic effect of the skeletal muscle-specific biochemical and topographical cues. In particular, the increase of the gene-expression levels of the dECM structure with topographical cues was approximately 1.5-1.8-fold compared with those of a gelatin methacrylate (GelMA)-based structure with the same topographical cues and a dECM-based structure without topographical cues. According to these in vitro cellular responses, the 3D printed dECM-based structures with topographical cues have the potential for bioengineering functional skeletal muscle tissues, and this strategy can be extended for many musculoskeletal tissues, such as tendons and ligaments and utilized for developing in vitro tissue-on-a-chip models in drug screening and development.
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“This process ensures myoblast alignment and differentiation, crucial for myotube formation, by employing UV light for crosslinking and removing PVA post‐printing.[ 158 ]”
From Bioactive scaffolds for tissue engineering: A review of decellularized extracellular matrix applications and innovations (2025) · cites this paper as [158]
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“This process ensures myoblast alignment and differentiation, crucial for myotube formation, by employing UV light for crosslinking and removing PVA post‐printing.[ 158 ]”
From Bioactive scaffolds for tissue engineering: A review of decellularized extracellular matrix applications and innovations (2025) · cites this paper as [158]
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“Similarly, methacrylated dECM from porcine skeletal muscle, when combined with sacrificial fibrillated PVA, has been bioprinted into aligned skeletal muscle structures.”
From Bioactive scaffolds for tissue engineering: A review of decellularized extracellular matrix applications and innovations (2025) · cites this paper as [158]
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3D bioprinting of tissues and organs
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Kim, B. S., Das, S., Jang, J., & Cho, D.-W. (2020) · Chemical Reviews · doi:10.1021/acs.chemrev.9b00808 · Cited by 465
Extracellular matrix: an important regulator of cell functions and skeletal muscle development
Zhang, W., Liu, Y., & Zhang, H. (2021) · Cell & Bioscience · doi:10.1186/s13578-021-00579-4 · Cited by 289
Golebiowska, A. A., Intravaia, J. T., Sathe, V. M., Kumbar, S. G., & Nukavarapu, S. P. (2024) · Bioactive Materials · doi:10.1016/j.bioactmat.2023.09.017 · Cited by 236
Designing Decellularized Extracellular Matrix‐Based Bioinks for 3D Bioprinting
Abaci, A., & Güvendiren, M. (2020) · Advanced Healthcare Materials · doi:10.1002/adhm.202000734 · Cited by 184
3D bioprinting: current status and trends—a guide to the literature and industrial practice
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Metadata
- Authors
- Kim, W., Lee, H., Lee, J., Atala, A., Yoo, J. J., Lee, S. J., & Kim, G. H.
- Affiliations
- Wake Forest University Health Sciences (US)
- Corresponding author
- Lee, Sang Jin
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2020-02
- Volume
- 230
- Pages
- 119632
- ISSN
- 0142-9612 (ISSN-L)
- PMC
- PMC7141931
- OpenAlex
- W2991322883
- Cited by
- 185
- References
- 55
- Citations by year
- 2026: 13 · 2025: 21 · 2024: 32 · 2023: 33 · 2022: 33 · 2021: 36 · 2020: 16
- FWCI
- 20.55
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Research Foundation of Korea
- Topics
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Keywords
- myotube formation, 3D bioprinting, decellularized extracellular matrix, skeletal muscle tissue engineering, uniaxial alignment, microtopography, myogenesis, C2C12 myoblasts, porcine skeletal muscle, gelatin methacryloyl, gene expression
- MeSH terms
- Animals, Cues, Extracellular Matrix, Swine, Muscle Fibers, Skeletal, Tissue Engineering, Bioprinting, Printing, Three-Dimensional
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