Heart-On-A-Chip Model Development Service

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More recently, Creative Biolabs has translated knowledge gained from cardiac tissue engineering with precision fabrication techniques to create physiologically relevant microfluidic models of the human heart for applications in drug discovery, cardiac regeneration, and prediction of drug response.

Microenvironment and Key Features of Heart

The heart has four main chambers, and during the development of its structure and organization, specific cell populations are assembled in different parts of the heart. 50-60% of the heart's entire cell population are cardiac fibroblasts, which build the extracellular matrix of the heart wall. The myocardium is mainly composed of cardiomyocytes, which are arranged in parallel and formed by fascial adherens junctions to form myocardial fibers responsible for spontaneous contraction. The cell groups on the endocardium and heart valves are mainly endothelial cells, the pericardial wall contains abundant epicardial cells. Furthermore, the immune response in the heart is balanced by macrophages, which are responsible for controlling cell numbers and maintaining the homeostasis of the extracellular matrix. As one of the most important organs in the human body, the proliferative potential of mature cardiomyocytes is very limited, and the arrangement of cardiomyocytes in the native heart complicates the parameters required to engineer cardiac tissue, making the design of functional heart substitutes extremely challenging.

Fig 1. Heart-on-a-Chip is widely used in the study of cardiac physiology and pathology. (Paloschi, 2021)

Typical Heart-On-A-Chip Models

Cardiotoxicity and heart disease studies are often conducted with long-term static culture and animal models, however oversimplified static culture models cannot reproduce in vivo counterparts to provide accurate predictions, animal models have shown overall ineffectiveness in predicting drug response in humans. It can be said that the lack of in vitro research models has led to the time-consuming, expensive, and often ineffective process of cardiac drug development. Here at Creative Biolabs, we currently offer a standardized bilayer microfluidic heart chip with upper and lower channels separated by a basement membrane, allowing mesenchymal cells to be cultured in the hydrogel while endothelial cells are individually exposed to physiological shear stress. Although simplified, the model still effectively mimics cardiac tissue architecture and recapitulates cell-cell/matrix interactions in vivo. In addition, the microfluidic environment can also reproduce the overall cardiac differentiation process from human pluripotent stem cells to cardiomyocytes through the precise regulation of molecular signals.

Fig 2. iPSCs can be induced to generate cardiac microtissues on chip. (Abulaiti, 2020)

Advanced Heart-On-A-Chip Models

Advances in precision fabrication platforms and tissue engineering technologies have allowed us to precisely control cell distribution, adhesion, morphology, structure, and geometry in microfluidic devices. By applying cyclic mechanical strain, shear stress, and appropriate electrical stimuli within the microfluidic chamber, cells are exposed to cues that mimic those experienced under physiological conditions. The combination of elastic film with good biocompatibility and cardiomyocytes realize the beating of cardiomyocytes through vacuum operation or electrical stimulation.

Fig 3. Pulsating pump recreates the regular beating of the heart. (Cruz-Moreira, 2021)

The implantation of on-chip peristaltic pumps or electrical components also allows the researchers to automatically and finely control the flow of fluid in the channels of the heart chip, thereby simulating the mechanical stimulation of the cells caused by the pulse of the heart. Diseases such as myocardial infarction will produce hypoxia, which will cause myocardial damage. Therefore, it is also feasible to use a heart chip to achieve non-uniform and long-term oxygen distribution to explore the electrophysiological response under myocardial hypoxia. As one of the most complex organs in the human body, the heart is unrealistic to reproduce all its functions through a single chip design. Creative Biolabs is more than capable of using our professional knowledge to help you design, develop and produce advanced heart-on-a-chip models suitable for your experimental needs.

Fig 4. Customized heart chips can meet the needs of all aspects of the experiment. (Yang, 2021)

Our Services

Tissue engineering experience and advanced microfabrication platform allow Creative Biolabs to build biologically relevant miniature human heart chips for our customers. Our standardized heart chip simulates the physiological and biological characteristics of the heart in vivo, which can be used to explore the effects of drug stimulation on heart tissue and predict the drug response of the human body. We also develop and customize bionic heart microfluidic chips for clients to reproduce organ functions. Tailor-made human heart-on-a-chip induced by various cardiac cell lines or iPSCs will be your best resource and high-sensitivity bioassay system for preclinical drug discovery and cardiotoxicity safety testing, so don’t hesitate to contact us for more information.

References

Paloschi, V.; et al. Organ-on-a-chip technology: a novel approach to investigate cardiovascular diseases. Cardiovascular Research. 2021, 117: 2742-2754.
Abulaiti, M.; et al. Establishment of a heart‑on‑a‑chip microdevice based on human iPS cells for the evaluation of human heart tissue function. Nature. 2020, 10: 19201.
Cruz-Moreira, D.; et al. Assessing the influence of perfusion on cardiac microtissue maturation: A heart‐on‐chip platform embedding peristaltic pump capabilities. Biotechnology Bioengineering. 2021, 118: 3128-3137.
Yang, Q.Z.; et al. Fabrication and biomedical applications of Heart-on-a-chip. International Journal of Bioprint. 2021, 7(3): 370.

For Research Use Only. Not For Clinical Use.