Automated perfused heart-on-a-chip mimicking cardiac micro-tissue maturation and function

How can organ-on-a-chip improve cardiac microtissue maturation and function? Recapitulating complex myocardial tissue has always been challenging due to its complex biochemical and biophysical characteristics. This is a recent paper from Moreira et al. at the polytechnic university of Milan where the authors study how the perfusion of culture medium at different rates affects cardiac microtissue maturation and function using a heart-on-a-chip.

The introduction of physical stimulation has made progress in cardiomyocytes culture, but the area still lacks the fundamental impactful controlled medium refreshment. In this experimental study, perfusion of culture medium next to a fibrin gel containing cardiomyocytes in a heart-on-a-chip not only delivers oxygen and essential nutrition for cardiomyocytes, but also prevents hypoxia in this dense micro-tissue. In addition, this engineered biological system offers the opportunity to understand the impact of the frequency of culture refreshment on cell development using an automatic on-chip micro-pump. It was observed that increasing the perfusion rate in the on-chip cardiac myocytes improved morphological maturation and contraction velocity remarkably.

This study has proven that all these noticeable changes are related to the significant alteration in the expression of a set of key genes at the molecular level in high flow rate conditions. In conclusion, this organ-on-a-chip provides a promising platform for adjusting medium perfusion accurately by an on-chip valve-based control system. This microsystem sheds light on cardiac microtissue modeling by making it morphologically and functionally closer to the native heart tissue. 

Strong points:
+ Enhancement of structural and functional maturation in cardiac microtissue
+ Automatic perfusion
+ Established and robust protocol for culturing cardiomyocytes between two microfluidic channels
+ Great potential to scale up the system

Nothing is perfect, the system can still be improved:
– No quantitative data around the tissue morphology and ECM remodeling
– No data on how well nutrients diffuse into the gel at different flow rates
– The same old story about PDMS, not the best material to use for testing drugs and small hydrophobic molecules in such a system.

Contact us if you want to know more about this system or similar technologies.

Link to paper: https://onlinelibrary.wiley.com/doi/abs/10.1002/bit.27836.

heart-on-a-chip, cardiac microtissue, microtissue maturation, tissue engineering, cardiac function, valve-based micro-pump, perfusion, microfluidic

Citation: Cruz‐Moreira, D., et al., Assessing the influence of perfusion on cardiac microtissue maturation: A heart‐on‐chip platform embedding peristaltic pump capabilities. Biotechnology and Bioengineering, 2021. 118(8): p. 3128-3137.

This article is reproduced under https://creativecommons.org/licenses/by/4.0/
The images in this post were modified for better clarity (part of the chip was  deleted) and the data were processed by AZAR Innovations