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Assessing the influence of perfusion on cardiac microtissue maturation: A heart‐on‐chip platform embedding peristaltic pump capabilities
Author(s) -
CruzMoreira Daniela,
Visone Roberta,
VasquesNóvoa Francisco,
S. Barros António,
LeiteMoreira Adelino,
Redaelli Alberto,
Moretti Matteo,
Rasponi Marco
Publication year - 2021
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.27836
Subject(s) - organ on a chip , microbiology and biotechnology , peristaltic pump , tissue engineering , biology , biomedical engineering , computational biology , nanotechnology , microfluidics , engineering , materials science , mechanical engineering
Heart‐on‐chip is an unprecedented technology for recapitulating key biochemical and biophysical cues in cardiac pathophysiology. Several designs have been proposed to improve its ability to mimic the native tissue and establish it as a reliable research platform. However, despite mimicking one of most vascularized organs, reliable strategies to deliver oxygen and substrates to densely packed constructs of metabolically demanding cells remain unsettled. Herein, we describe a new heart‐on‐chip platform with precise fluid control, integrating an on‐chip peristaltic pump, allowing automated and fine control over flow on channels flanking a 3D cardiac culture. The application of distinct flow rates impacted on temporal dynamics of microtissue structural and transcriptional maturation, improving functional performance. Moreover, a widespread transcriptional response was observed, suggesting flow‐mediated activation of critical pathways of cardiomyocyte structural and functional maturation and inhibition of cardiomyocyte hypoxic injury. In conclusion, the present design represents an important advance in bringing engineered cardiac microtissues closer to the native heart, overcoming traditional bulky off‐chip fluid handling systems, improving microtissue performance, and matching oxygen and energy substrate requirements of metabolically active constructs, avoiding cellular hypoxia. Distinct flow patterns differently impact on microtissue performance and gene expression program.