Maladaptive Contractility of 3D Human Cardiac Microtissues to Mechanical Nonuniformity.

Chenyan Wang, Sangmo Koo, Minok Park, Zacharias Vangelatos, Plansky Hoang, Bruce R Conklin, Costas P Grigoropoulos, Kevin E Healy, Zhen Ma
Author Information
  1. Chenyan Wang: Department of Biomedical & Chemical Engineering, Syracuse Biomaterials Institute, Syracuse University, Syracuse, NY, 13210, USA.
  2. Sangmo Koo: Department of Mechanical Engineering, University of California, Berkeley, CA, 94720, USA.
  3. Minok Park: Department of Mechanical Engineering, University of California, Berkeley, CA, 94720, USA.
  4. Zacharias Vangelatos: Department of Mechanical Engineering, University of California, Berkeley, CA, 94720, USA.
  5. Plansky Hoang: Department of Biomedical & Chemical Engineering, Syracuse Biomaterials Institute, Syracuse University, Syracuse, NY, 13210, USA.
  6. Bruce R Conklin: Gladstone Institute of Cardiovascular Diseases, University of California, San Francisco, CA, 94158, USA.
  7. Costas P Grigoropoulos: Department of Mechanical Engineering, University of California, Berkeley, CA, 94720, USA.
  8. Kevin E Healy: Department of Bioengineering, University of California, Berkeley, CA, 94720, USA.
  9. Zhen Ma: Department of Biomedical & Chemical Engineering, Syracuse Biomaterials Institute, Syracuse University, Syracuse, NY, 13210, USA. ORCID

Abstract

Cardiac tissues are able to adjust their contractile behavior to adapt to the local mechanical environment. Nonuniformity of the native tissue mechanical properties contributes to the development of heart dysfunctions, yet the current in vitro cardiac tissue models often fail to recapitulate the mechanical nonuniformity. To address this issue, a 3D cardiac microtissue model is developed with engineered mechanical nonuniformity, enabled by 3D-printed hybrid matrices composed of fibers with different diameters. When escalating the complexity of tissue mechanical environments, cardiac microtissues start to develop maladaptive hypercontractile phenotypes, demonstrated in both contractile motion analysis and force-power analysis. This novel hybrid system could potentially facilitate the establishment of "pathologically-inspired" cardiac microtissue models for deeper understanding of heart pathology due to nonuniformity of the tissue mechanical environment.

Keywords

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Grants

  1. 16POST27750031/American Heart Association-American Stroke Association
  2. R01 HL096525/NHLBI NIH HHS
  3. R01 HL108677/NHLBI NIH HHS
  4. UH3 TR000487/NCATS NIH HHS

MeSH Term

Heart
Humans
Mechanical Phenomena
Muscle Contraction
Tissue Engineering

Word Cloud

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