Past efforts to replicate in vivo cardiac tissue environments have proven to be challenging due to difficulties when mimicking contractility and electrophysiological responses. Such features would greatly increase the accuracy of in vitro experiments.
Microfluidics has already contributed to in vitro experiments on cardiomyocytes, which generate the electrical impulses that control the heart rate. For instance, researchers have built an array of PDMS microchambers, aligned with sensors and stimulating electrodes as a tool that will electrochemically and optically monitor the cardiomyocytes' metabolism. Another lab-on-a-chip similarly combined a microfluidic network in PDMS with planar microelectrodes, this time to measure extracellular potentials from single adult murine cardiomyocytes.
A reported design of a heart-on-a-chip claims to have built "an efficient means of measuring structure-function relationships in constructs that replicate the hierarchical tissue architectures of laminar cardiac muscle."  This chip determines that the alignment of the myocytes in the contractile apparatus made of cardiac tissue and the gene expression profile (affected by shape and cell structure deformation) contributes to the force produced in cardiac contractility. This heart-on-a-chip is a biohybrid construct: an engineered anisotropic ventricular myocardium is an elastomeric thin film.
The design and fabrication process of this particular microfluidic device entails first covering the edges of a glass surface with tape (or any protective film) such as to contour the substrate's desired shape. A spin coat layer of PNIPA is then applied. After its dissolution, the protective film is peeled away, resulting in a self-standing body of PNIPA. The final steps involve the spin coating of protective surface of PDMS over the cover slip and curing. Muscular thin films (MTF) enable cardiac muscle monolayers to be engineered on a thin flexible substrate of PDMS. In order to properly seed the 2D cell culture, a microcontact printing technique was used to lay out a fibronectin "brick wall" pattern on the PDMS surface. Once the ventricular myocytes were seeded on the functionalized substrate, the fibronectin pattern oriented them to generate an anisotropic monolayer.
After the cutting of the thin films into two rows with rectangular teeth, and subsequent placement of the whole device in a bath, electrodes stimulate the contraction of the myocytes via a field-stimulation – thus curving the strips/teeth in the MTF. Researchers have developed a correlation between tissue stress and the radius of curvature of the MTF strips during the contractile cycle, validating the demonstrated chip as a "platform for quantification of stress, electrophysiology and cellular architecture."
While researchers have focused on 2D cell cultures, 3D cell constructs mimic the in vivo environment and the interactions (e.g., cell to cell) occurring in the human body better. Hence, they are considered promising models for studies such as toxicology and response to drugs. Based on the study of Chen et al., the interactions of valvular endothelial/interstitial cells (VECs/VICs) are studied via a 3D PDMS-glass microfluidic device with a top channel flowed with VECs under shear stress, a membrane with uniform pores, and a bottom channel containing VIC-hydrogel. VECs are verified to restrain the differentiation of morbid VIC myofibroblast, with reinforced suppression by shear stress.
Another PDMS 3D microfluidic heart-on-a-chip design is measured to generate 10% to 15% of uniaxial cyclic mechanical strains. The device consists of a cell culture with hanging posts for caging and an actuation compartment with scaffolding posts to avoid buckling of PDMS, along with the cardiac cycle pressure signal imitation. The neonatal rat micro-engineered cardiac tissues (μECTs) stimulated by this design show improved synchronous beating, proliferation, maturation, and viability compared to the unstimulated control. The contraction rate of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) is observed to accelerate with 100-fold less isoprenaline, a heart block treatment, when having electrical pacing signal (+ES) compared to that without ES.
3D microfluidic heart-on-a-chips have also facilitated the research of heart diseases. For instance, cardiac hypertrophy and fibrosis are studied via the respective biomarker level of the mechanically stimulated μECTs, such as atrial natriuretic peptide (ANP) for the former and transforming growth factor-β (TGF-β) for the latter. Also, the knowledge of ischaemia is gained by action potential observations.
The microfluidic approaches utilized for teasing apart specific mechanisms at the single-cell level and at the tissue-level are becoming increasingly sophisticated and so are the fabrication methods. Rapid dissemination and availability of low cost, high resolution 3D printing technology is revolutionizing this space and opening new possibilities for building patient specific heart and cardiovascular systems. The confluence of high resolution 3D printing, patient derived iPSCs with artificial intelligence is posed to make significant strides towards truly personalized heart modelling and ultimately, patient care.