Toward Hierarchical Assembly of Aligned Cell Sheets into a Conical Cardiac Ventricle Using Microfabricated Elastomers
Open accessAbstract
Despite current efforts in organ‐on‐chip engineering to construct miniature cardiac models, they often lack some physiological aspects of the heart, including fiber orientation. This motivates the development of bioartificial left ventricle models that mimic the myofiber orientation of the native ventricle. Herein, an approach relying on microfabricated elastomers that enables hierarchical assembly of 2D aligned cell sheets into a functional conical cardiac ventricle is described. Soft lithography and injection molding techniques are used to fabricate micro‐grooves on an elastomeric polymer scaffold with three different orientations ranging from −60° to +60°, each on a separate trapezoidal construct. The width of the micro‐grooves is optimized to direct the majority of cells along the groove direction and while periodic breaks are used to promote cell–cell contact. The scaffold is wrapped around a central mandrel to obtain a conical‐shaped left ventricle model inspired by the size of a human left ventricle 19 weeks post‐gestation. Rectangular micro‐scale holes are incorporated to alleviate oxygen diffusional limitations within the 3D scaffold. Cardiomyocytes within the 3D left ventricle constructs showed high viability in all layers after 7 days of cultivation. The hierarchically assembled left ventricle also provided functional readouts such as calcium transients and ejection fraction.
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- Authors
- Mohammadi, M. H., Okhovatian, S., Savoji, H., Campbell, S. B., Lai, B. F. L., Wu, J., Pascual‐Gil, S., Bannerman, D., Rafatian, N., Li, R., & Radisic, M.
- Affiliations
- University of Toronto (CA)
- CHU Sainte-Justine Research Center (CA)
- University Health Network (CA)
- Corresponding author
- Radisic, Milica
- ORCID
- Venue
- Advanced Biology
- Publisher
- Wiley
- Published
- 2022-07-07
- Volume
- 6
- Issue
- 11
- Pages
- e2101165-e2101165
- ISSN
- 2701-0198 (ISSN-L)
- PMC
- PMC9691564
- OpenAlex
- W4284897378
- Cited by
- 28
- References
- 68
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 4 · 2023: 12 · 2022: 1
- FWCI
- 1.67
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Advanced Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- PolyPublie (École Polytechnique de Montréal) (submittedVersion)
- Funders
- National Institutes of Health (2r01hl076485-16)
- National Heart, Lung, and Blood Institute (R01-HL076485)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Keywords
- myofiber orientation, soft lithography, injection molding, cardiomyocyte viability, calcium transients, ejection fraction, organ-on-a-chip, oxygen diffusion, hierarchical assembly
- MeSH terms
- Heart Ventricles, Humans, Elastomers, Tissue Engineering, Myocytes, Cardiac, Tissue Scaffolds
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