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 used in the study of cardiac physiology and pathology.1,4
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.2,4
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.3,4
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.
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.
Features and Benefits
Physiological Realism
The Heart-On-A-Chip model replicates human heart functions, including electrical activity and mechanical contractions. This realism provides a more accurate platform for studying cardiac behavior and testing drug effects compared to traditional 2D cell cultures or animal models.
Customizable Microenvironment
Researchers can tailor the Heart-On-A-Chip model to specific experimental needs by adjusting factors like cell types, mechanical properties, and microchannel design. This customization supports a wide range of applications, from basic research to personalized medicine.
Real-Time Monitoring
The integration of sensors within the Heart-On-A-Chip allows for real-time monitoring of cellular responses and environmental conditions. This feature provides valuable insights into the dynamic processes occurring within the cardiac tissues.
High Sensitivity to Drug Responses
The model's ability to mimic the heart's natural environment allows for the detection of subtle drug effects on cardiac cells. This high sensitivity helps identify potential side effects and optimize therapeutic dosages.
Reduced Animal Testing
By providing a more accurate representation of human heart physiology, the Heart-On-A-Chip model reduces the reliance on animal testing. This not only addresses ethical concerns but also improves the relevance of preclinical studies to human health.
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.
under Open Access license CC BY 4.0, without modification.
Q&As
Q: How does the Heart-On-A-Chip model simulate heart functions?
A: The model simulates heart functions by incorporating mechanical and electrical stimuli to mimic the natural heartbeat. This includes cyclic stretching to replicate the contraction and relaxation of heart muscles, providing a more accurate representation of cardiac physiology.
Q: What are the key components of the Heart-On-A-Chip model?
A: The Heart-On-A-Chip model typically consists of microchannels and chambers made from biocompatible materials like PDMS. These channels house heart cells and mimic the structure and function of human heart tissues, including electrical activity and mechanical contractions.
Q: What types of research can benefit from the Heart-On-A-Chip model?
A: The Heart-On-A-Chip model is beneficial for various research areas, including cardiotoxicity testing, disease modeling, regenerative medicine, and the study of drug interactions with cardiac tissues. It offers a versatile platform for both basic and applied research.
Q: How does the model facilitate high-throughput screening?
A: The Heart-On-A-Chip model is designed to support high-throughput screening by allowing the simultaneous testing of multiple drug candidates. This accelerates the drug discovery process and helps identify effective therapies more efficiently.
Q: Can the Heart-On-A-Chip model be customized?
A: Yes, the Heart-On-A-Chip model can be customized to meet specific research needs. Researchers can modify the cell types, extracellular matrix components, and mechanical properties to study different cardiac conditions or test specific drug.
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Creative Biolabs has established a comprehensive microfluidics technique platform.
Fig. 1 Heart-on-a-Chip used in the study of cardiac physiology and pathology.1,4
Fig. 2 iPSCs can be induced to generate cardiac microtissues on chip.2,4
Fig. 3 Pulsating pump recreates the regular beating of the heart.3,4
