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Design and Fabrication of Biological Wires for Cardiac Fibrosis Disease Modeling

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Cardiac Tissue Engineering

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2485))

Abstract

Extensive progress has been made in developing engineered models for elucidating human cardiac disease. Cardiac fibrosis is often associated with all forms of cardiac disease and has a direct deleterious effect on cardiac function. As currently there is no effective therapeutic strategy specifically designed to target fibrosis, in vitro diagnostic platforms for drug testing have generated significant interest. In this context, we have developed an innovative approach to generate human cardiac fibrotic tissues on Biowire II platform and established a compound screening system. The disease model is constructed to recapitulate contractile, biomechanical, and electrophysiological complexities of fibrotic myocardium. Additionally, an integrated model with fibrotic and healthy cardiac tissues coupled together can be created to mimic focal fibrosis. The methods for constructing the Biowire fibrotic model will be described here.

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References

  1. Leask A (2015) Getting to the heart of the matter: new insights into cardiac fibrosis. Circ Res 116:1269–1276

    Article  CAS  Google Scholar 

  2. Ahadian S, Civitarese R, Bannerman D, Mohammadi MH, Lu R, Wang E, Davenport-Huyer L, Lai B, Zhang B, Zhao Y, Mandla S, Korolj A, Radisic M (2018) Organ-on-a-chip platforms: a convergence of advanced materials, cells, and microscale technologies. Adv Healthc Mater 7(2):1700506. https://doi.org/10.1002/adhm.201700506

    Article  CAS  Google Scholar 

  3. Savoji H, Mohammadi MH, Rafatian N, Toroghi MK, Wang EY, Zhao Y, Korolj A, Ahadian S, Radisic M (2019) Cardiovascular disease models: a game changing paradigm in drug discovery and screening. Biomaterials 198:3–26. https://doi.org/10.1016/j.biomaterials.2018.09.036

    Article  CAS  PubMed  Google Scholar 

  4. Asmani M, Velumani S, Li Y, Wawrzyniak N, Hsia I, Chen Z, Hinz B, Zhao R (2018) Fibrotic microtissue array to predict anti-fibrosis drug efficacy. Nat Commun 9(1):2066. https://doi.org/10.1038/s41467-018-04336-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Sadeghi AH, Shin SR, Deddens JC, Fratta G, Mandla S, Yazdi IK, Prakash G, Antona S, Demarchi D, Buijsrogge MP, Sluijter JPG, Hjortnaes J, Khademhosseini A (2017) Engineered 3D cardiac fibrotic tissue to study fibrotic remodeling. Adv Healthc Mater 6(11). https://doi.org/10.1002/adhm.201601434

  6. Wang EY, Rafatian N, Zhao Y, Lee A, Lai BFL, Lu RX, Jekic D, Davenport Huyer L, Knee-Walden EJ, Bhattacharya S, Backx PH, Radisic M (2019) Biowire model of interstitial and focal cardiac fibrosis. ACS Central Sci 5(7):1146–1158. https://doi.org/10.1021/acscentsci.9b00052

    Article  CAS  Google Scholar 

  7. Zhao Y, Rafatian N, Feric NT, Cox BJ, Aschar-Sobbi R, Wang EY, Aggarwal P, Zhang B, Conant G, Ronaldson-Bouchard K, Pahnke A, Protze S, Lee JH, Davenport Huyer L, Jekic D, Wickeler A, Naguib HE, Keller GM, Vunjak-Novakovic G, Broeckel U, Backx PH, Radisic M (2019) A platform for generation of chamber-specific cardiac tissues and disease modeling. Cell 176(4):913–927. e918. https://doi.org/10.1016/j.cell.2018.11.042

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Zhao Y, Wang EY, Davenport LH, Liao Y, Yeager K, Vunjak-Novakovic G, Radisic M, Zhang B (2019) A multimaterial microphysiological platform enabled by rapid casting of elastic microwires. Adv Healthc Mater 8(5):1801187. https://doi.org/10.1002/adhm.201801187

    Article  CAS  Google Scholar 

  9. Tandon N, Cannizzaro C, Chao P-HG, Maidhof R, Marsano A, Au HTH, Radisic M, Vunjak-Novakovic G (2009) Electrical stimulation systems for cardiac tissue engineering. Nat Protoc 4(2):155–173. https://doi.org/10.1038/nprot.2008.183

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Sahin O, Ashokkumar M, Ajayan PM (2018) 3-Micro- and nanopatterning of biomaterial surfaces. In: Balakrishnan SMS, Thomas S (eds) Fundamental biomaterials: metals. Woodhead Publishing, pp 67–78. https://doi.org/10.1016/B978-0-08-102205-4.00003-9

    Chapter  Google Scholar 

  11. Montgomery M, Davenport Huyer L, Bannerman D, Mohammadi MH, Conant G, Radisic M (2018) Method for the fabrication of elastomeric polyester scaffolds for tissue engineering and minimally invasive delivery. ACS Biomater Sci Eng 4(11):3691–3703. https://doi.org/10.1021/acsbiomaterials.7b01017

    Article  CAS  PubMed  Google Scholar 

  12. Zhang B, Lai BFL, Xie R, Davenport Huyer L, Montgomery M, Radisic M (2018) Microfabrication of AngioChip, a biodegradable polymer scaffold with microfluidic vasculature. Nat Protoc 13(8):1793–1813. https://doi.org/10.1038/s41596-018-0015-8

    Article  CAS  PubMed  Google Scholar 

  13. Lian X, Hsiao C, Wilson G, Zhu K, Hazeltine LB, Azarin SM, Raval KK, Zhang J, Kamp TJ, Palecek SP (2012) Robust cardiomyocyte differentiation from human pluripotent stem cells via temporal modulation of canonical Wnt signaling. Proc Natl Acad Sci U S A 109(27):E1848–E1857. https://doi.org/10.1073/pnas.1200250109

    Article  PubMed  PubMed Central  Google Scholar 

  14. Davenport Huyer L, Zhang B, Korolj A, Montgomery M, Drecun S, Conant G, Zhao Y, Reis L, Radisic M (2016) Highly elastic and moldable polyester biomaterial for cardiac tissue engineering applications. ACS Biomater Sci Eng 2(5):780–788. https://doi.org/10.1021/acsbiomaterials.5b00525

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We thank Drs. Yimu Zhao, Locke Davenport Huyer, and Boyang Zhang who established the initial methods of Biowire II platform design and polymer synthesis on which this chapter was based.

Some components of schematics were created with BioRender.com.

Radisic lab is funded by the Heart and Stroke Foundation Grant-in-Aid (G-16-00012711), Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant (RGPIN 326982-10), NSERC-CIHR Collaborative Health Research Grant (CHRP 493737-16), and National Institutes of Health Grant 2R01 HL076485. MR was supported by NSERC Steacie Fellowship and Canada Research Chair, LDH was supported by CIHR Vanier Scholarship. The authors acknowledge the Canada Foundation for Innovation, Project 19119, and the Ontario Research Fund for funding of the Centre for Spectroscopic Investigation of Complex Organic Molecules and Polymers.

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Correspondence to Milica Radisic .

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Wang, E.Y., Smith, J., Radisic, M. (2022). Design and Fabrication of Biological Wires for Cardiac Fibrosis Disease Modeling. In: Coulombe, K.L., Black III, L.D. (eds) Cardiac Tissue Engineering. Methods in Molecular Biology, vol 2485. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2261-2_12

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  • DOI: https://doi.org/10.1007/978-1-0716-2261-2_12

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-2260-5

  • Online ISBN: 978-1-0716-2261-2

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