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.

Results
The engineered heart-on-a-chip of this study 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 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. This microsystem sheds light on cardiac microtissue modeling by making it morphologically and functionally closer to the native heart tissue. 

Method
The microfluidics platform consists of a cell culture layer and a pressure-actuated control layer, cardiomyocytes (Neonatal rat ventricular myocytes (NRVM)) were suspended in fibrin gel.
Fabrication method: Soft lithography with PDMS
Cell incorporation: Cell-laden fibrin gel was injected in the cell culture channel of the fluidic chamber
Perfusion/refreshing method: Perfusion with on-chip peristaltic pump
On-chip read-outs: End-point microscopy
Off-chip read-outs: Real time-qPCR

Strong points:
+ Enhancement of structural and functional maturation in cardiac microtissue
+ Automatic and adjustable medium perfusion by an on-chip valve-based control system.
+ Established and robust protocol for culturing cardiomyocytes between two microfluidic channels
+ Great potential to scale up the system
+ Delivering oxygen and essential nutrition to cardiomyocytes by the perfusion

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.

Conclusion and outlook
The microfluidic heart-on-a-chip in this study allows simultaneous fine-control of different perfusion profiles and the study of their effects on tissue function and maturation. The compatibility of the presented platform allows further integration with other relevant features (e.g., uniaxial cyclic strain and electrical stimulation).

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.

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