Abstract
Organs-on-chip technology has recently emerged as a promising tool to generate advanced cardiac tissue in vitro models, by recapitulating key physiological cues of the native myocardium. Biochemical, mechanical, and electrical stimuli have been investigated and demonstrated to enhance the maturation of cardiac constructs. However, the combined application of such stimulations on 3D organized constructs within a microfluidic platform was not yet achieved. For this purpose, we developed an innovative microbioreactor designed to provide a uniform electric field and cyclic uniaxial strains to 3D cardiac microtissues, recapitulating the complex electro-mechanical environment of the heart. The platform encompasses a compartment to confine and culture cell-laden hydrogels, a pressure-actuated chamber to apply a cyclic uniaxial stretch to microtissues, and stainless-steel electrodes to accurately regulate the electric field. The platform was exploited to investigate the effect of two different electrical stimulation patterns on cardiac microtissues from neonatal rat cardiomyocytes: a controlled electric field [5 V/cm, or low voltage (LV)] and a controlled current density [74.4 mA/cm2, or high voltage (HV)]. Our results demonstrated that LV stimulation enhanced the beating properties of the microtissues. By fully exploiting the platform, we combined the LV electrical stimulation with a physiologic mechanical stretch (10% strain) to recapitulate the key cues of the native cardiac microenvironment. The proposed microbioreactor represents an innovative tool to culture improved miniaturized cardiac tissue models for basic research studies on heart physiopathology and for drug screening.
Highlights
As key requirements to regulate cell behaviors and enhance cell function.3,4 miniaturization offers several advantages in biology, such as a significant reduction in the use of reagents and cells, allowing for increased experimental throughput in a cost-effective manner
We developed an innovative microbioreactor designed to provide a uniform electric field and cyclic uniaxial strains to 3D cardiac microtissues, recapitulating the complex electro-mechanical environment of the heart
To merge the advantages of microfluidic platforms with the potentiality of enhancing tissue properties by means of mechanical stimulation, our group developed for the first time an innovative microfluidic platform providing cardiac microtissues with a cyclic mechanical deformation, mimicking the contraction-relaxation phases experienced by cells in vivo
Summary
As key requirements to regulate cell behaviors and enhance cell function. miniaturization offers several advantages in biology, such as a significant reduction in the use of reagents and cells, allowing for increased experimental throughput in a cost-effective manner.. Miniaturization offers several advantages in biology, such as a significant reduction in the use of reagents and cells, allowing for increased experimental throughput in a cost-effective manner.5,6 By exploiting this technology, great effort has been made to develop robust in vitro cardiac models to provide better insights into heart physiology and pathology in an economically sustainable way.. Cardiomyocytes (CMs) in vivo contract in a coordinated fashion, generating a continuous cyclic mechanical stretch.13–15 This deformation activates mechanosensitive signaling pathways, which positively affect CM properties and functionality.. To merge the advantages of microfluidic platforms with the potentiality of enhancing tissue properties by means of mechanical stimulation, our group developed for the first time an innovative microfluidic platform providing cardiac microtissues with a cyclic mechanical deformation, mimicking the contraction-relaxation phases experienced by cells in vivo.. These works have some limitations as follows: (i) a non-uniform electric field on the cell constructs, due to the lack of ad hoc integrated electrical systems, and (ii) the lack of consensus about an optimal electrical stimulation protocol for the generation of mature cardiac models, able to improve the spontaneous and synchronous cardiac beating.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
