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Structures of the heart-on-a-chip. A highly integrated heart-on-a-chip may include four components: microfluidic chips, microtissues, microactuators and microsensor.
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Heart diseases have become the main killer threatening human health, and various methods have been developed to study heart disease. Among them, heart-on-a-chip has emerged in recent years as a method for constructing disease (or normal) models in vitro and is considered as a promising tool to study heart diseases. Compared with other methods, the...
Context in source publication
Context 1
... reviewing the existing literature, we propose that a highly integrated heart-on-a-chip includes four elements: microfluidic chip, cells/microtissues, microactuators for physical/chemical stimuli, and microsensors for monitoring cells status (Figure 1). In practical experiments, a heart-on-a-chip may not include all these four elements, but the microfluidic chip and cells/microtissues are necessary. ...
Citations
... Принципиальная схема «сердца-на-чипе» («Heart-On-Chip») включает микрожидкостные чипы, клетки или микроткани, элементы для построения среды (микроактюаторы для физических или химических стимулов) и микросенсоры для считывания информации (рис. 2) [13]. Определенными сложностями в создании «сердца-на-чипе» являются необходимость воспроизведения сократительной способности и электрофизиологических реакций и их фиксация с помощью датчиков [14]. ...
... Рис. 2. Принципиальная схема «сердца-на-чипе» [13] Fig. 2. Principle scheme of "Heart-On-Chip" [13] 2024;39(1): [18][19][20][21][22][23][24][25][26][27] Для изучения ишемии / реперфузии миокарда разработаны модели «сердца-на-чипе», в которых осуществляется регуляция подачи кислорода [15]. Создание модели, имитирующей постинфарктные изменения, возможно путем воздействия повреждающих факторов (например, лазера) или регуляцией количества фибробластов и коллагена [16]. ...
... Рис. 2. Принципиальная схема «сердца-на-чипе» [13] Fig. 2. Principle scheme of "Heart-On-Chip" [13] 2024;39(1): [18][19][20][21][22][23][24][25][26][27] Для изучения ишемии / реперфузии миокарда разработаны модели «сердца-на-чипе», в которых осуществляется регуляция подачи кислорода [15]. Создание модели, имитирующей постинфарктные изменения, возможно путем воздействия повреждающих факторов (например, лазера) или регуляцией количества фибробластов и коллагена [16]. ...
Myocardial ischemia is the basis for many acute and chronic conditions with great social significance. Therefore, experimental models that describe ischemia development in humans are necessary for a better understanding of the pathophysiology of these conditions and the development of medical and surgical methods of treatment.
Aim: To compare current approaches to experimental modeling of myocardial ischemia considering the pathogenetic features of the simulated processes. The manuscript describes the main experimental models of myocardial ischemia: in vitro cellular models, ex vivo isolated heart models, in vivo animal models, the principal components of the ‘ heart-on-chip’ model and the possibilities of in silico modeling. The criteria for choosing a specific model of ischemia by pathophysiological approach, advantages and limitations of the models are considered.
... And by means of microsensors, microfluidic systems assist in monitoring cell status. This promotes assayperformance compared to other 3D modalities wherein cells are deeply embedded in 3D matrices [53]. ...
For recent decades, cardiac diseases have been the leading cause of death and morbidity worldwide. Despite significant achievements in their management, profound understanding of disease progression is limited. The lack of biologically relevant and robust preclinical disease models that truly grasp the molecular underpinnings of cardiac disease and its pathophysiology attributes to this stagnation, as well as the insufficiency of platforms that effectively explore novel therapeutic avenues. The area of fundamental and translational cardiac research has therefore gained wide interest of scientists in the clinical field, while the landscape has rapidly evolved towards an elaborate array of research modalities, characterized by diverse and distinctive traits. As a consequence, current literature lacks an intelligible and complete overview aimed at clinical scientists that focuses on selecting the optimal platform for translational research questions. In this review, we present an elaborate overview of current in vitro, ex vivo, in vivo and in silico platforms that model cardiac health and disease, delineating their main benefits and drawbacks, innovative prospects, and foremost fields of application in the scope of clinical research incentives.
... Previous review papers have extensively covered the evolution of heart-on-chip models. [26][27][28][29] Organ-on-a-chip models of the heart so far have each tended to focus upon a specific feature. The myocardium, or muscular layer of the heart, is of special interest. ...
Organ-on-a-chip devices are powerful modeling systems that allow researchers to recapitulate the in vivo structures of organs as well as the physiological conditions those tissues are subject to. These devices are useful tools in modeling not only the behavior of a healthy organ but also in modeling disease pathology or the effects of specific drugs. The incorporation of fluidic flow is of great significance in these devices due to the important roles of physiological fluid flows in vivo. Recent developments in the field have led to the production of vascularized organ-on-a-chip devices, which can more accurately reproduce the conditions observed in vivo by recapitulating the vasculature of the organ concerned. This review paper will provide a brief overview of the history of organ-on-a-chip devices, before discussing developments in the production of vascularized organs-on-chips, and the implications these developments hold for the future of the field.
... These elements include microfluidic chips, microtissues, microactuators for creating microenvironments, and microsensors for result readout. 76 To optimize the design of OoC channels, Li and colleagues developed a numerical model based on the Lagrange method that can detect the dynamic process and efficiencies of cell capture in three classical models, including U-shaped microchambers, side microchambers, and bottom microwells. 77 Park and coworkers introduced the advances in microfluidics and the creation of patterned microchannels through soft lithography techniques toward the 3D cell culture approach. ...
Cardiovascular disease (CVD) is currently a serious and growing public health problem. In tackling this challenge, organ‐on‐chip (OoC) technology, combined with cell culture and microfluidics, presents a powerful approach for constructing sophisticated tissue models in vitro that can simulate the physiological and pathological microenvironments of human organs. Nowadays, OoC technology has emerged as a pivotal tool in advancing our understanding of CVD pathogenesis, facilitating tissue regeneration studies, conducting efficient drug screening, and assessing therapeutic effects. Moreover, it offers a diverse array of study platforms for preclinical research, fostering innovative approaches towards combating CVD and improving patient outcomes. In this review, we first present the key advantages of OoC technology, including its highly relevant physiological microenvironment, incorporation of integrated functions, and the possibility of the construction of multiorgan‐on‐a‐chip through microfluidic linkage. Then, we summarized the role of OoC in the construction of disease pathological models, which provides a new channel for the exploration of disease pathological mechanisms. Moreover, we discuss the application of this technology in cardiac regeneration and drug screening. Finally, we discuss the challenges of tissue models constructed based on OoC technology and the prospects of this innovative approach.
... The common strategies of 3D bioprinting include inkjet-based bioprinting, extrusion-based bioprinting, and laser-assisted (e.g., stereolithography) bioprinting ( Figure 1) [8] . Over the past few decades, the field of 3D bioprinting has experienced significant advancements in terms of the types of tissue models that can be constructed, including cancer [9] , blood vessels [10,11] , heart [12] , and lungs [13,14] . Indeed, 3D bioprinting has the potential to offer various benefits and applications beyond just lung transplantation. ...
Lung tissue engineering (LTE) has gained significant attention as a highly promising and innovative strategy to tackle the formidable obstacles posed by lung-related diseases and the lack of compatible donor organs availability. In the realm of groundbreaking advancements in tissue engineering (TE), one particular technology that has emerged as a game-changer is three-dimensional (3D) bioprinting. It distinguishes itself by offering a potent and versatile approach to constructing intricate structures while opening up new horizons for TE and regenerative medicine (RM). This review focuses on the application of multiscale 3D bioprinting techniques in LTE and the reconstitution of lung tissue in vitro. We analyzed the key aspects such as bioink formulations and printing strategies utilized from macroscale 3D bioprinting to micro/nanoscale 3D bioprinting. Additionally, we evaluated the potential of multiscale bioprinting to replicate the complex architecture of the lung, ranging from macrostructures to micro/nanoscale features. We discussed the challenges and future directions in biofabrication approaches for LTE. Furthermore, we highlight the current progress and future perspectives in tissue reconstitution of lung in vitro, considering factors such as cell source, functionalization, and integration of physiological cues. Overall, multiscale 3D bioprinting offers exciting possibilities for the development of functional lung tissues, enabling disease modeling, new drug screening, and personalized regenerative therapies.
... One of the most crucial parts of the human body is the heart. In terms of soft lithography, PDMS is placed onto a readymade mould [15]. The PDMS slab is then adhered to the glass substrate after being hardened and pulled off from the mould. ...
... Cardiomyocytes are known to respond to electrophysiological stimulation. Cell synchronization and calcium processing can both benefit from electrical stimulation, which can also enhance the proportion of cells that beat spontaneously [15]. Electrical stimulation in a heart-on-a-chip typically takes place through electrodes in contact with cells. ...
... The fabrication of an elastic component in a heart-on-a-chip is one often employed technique. The CMs cultivated on the elastic component would result in the component's obvious deformation [15]. A microscope can see and record the deformation caused by the elastic component being bent by the contraction force of CMs. ...
A micro-physiological system is another term for an organ-on-a-chip. Due to the idea's widespread use in drug discovery, precision medicine, and drug screening, interest in it has increased recently. The primary message of this article is to illustrate how artificial drug proof can closely imitate the human body in every regard. Important work for a biomimetic system of physiological organs based on a microfluidic chip using cell biology, engineering, and biomaterials technology. In addition, the use and effectiveness of the gut-on-a-chip, liver-on-a-chip, lung-on-a-chip, and heart-on-a-chip are examined. We have discussed the current status of this project, OOC prospects for the future, and opportunities for microfluidic devices and organs on a chip in this section.
... These factors, coupled with the affordability and user-friendliness of chips, contribute to their increasing popularity as a promising approach in cardiac regeneration. With ongoing advancements and research in this field, it is expected that the use of chips for cardiac regeneration will continue to evolve and gain prominence in the coming years [349]. ...
Cardiac regeneration is a critical endeavor in the treatment of heart diseases, aimed at repairing and enhancing the structure and function of damaged myocardium. This review offers a comprehensive overview of current advancements and strategies in cardiac regeneration, with a specific focus on regenerative medicine and tissue engineering-based approaches. Stem cell-based therapies, which involve the utilization of adult stem cells and pluripotent stem cells hold immense potential for replenishing lost cardiomyocytes and facilitating cardiac tissue repair and regenera-tion. Tissue engineering also plays a prominent role employing synthetic or natural biomaterials, engineering cardiac patches and grafts with suitable properties, and fabricating upscale bioreactors to create functional constructs for cardiac recovery. These constructs can be transplanted into the heart to provide mechanical support and facilitate tissue healing. Additionally, the production of organoids and chips that accurately replicate the structure and function of the whole organ is an area of extensive research. Despite significant progress, several challenges persist in the field of cardiac regeneration. These include enhancing cell survival and engraftment, achieving proper vascularization, and ensuring the long-term functionality of engineered constructs. Overcoming these obstacles and offering effective therapies to restore cardiac function could improve the quality of life for individuals with heart diseases.
... These factors, coupled with the affordability and user-friendliness of chips, contribute to their increasing popularity as a promising approach in cardiac regeneration. With ongoing advancements and research in this field, it is expected that the use of chips for cardiac regeneration will continue to evolve and gain prominence in the coming years [308]. ...
Cardiac regeneration is a critical endeavor in the treatment of heart diseases, aimed at repairing and enhancing the structure and function of damaged myocardium. This review offers a comprehensive overview of current advancements and strategies in cardiac regeneration, with a specific focus on regenerative medicine and tissue engineering-based approaches. Stem cell-based therapies, which involve the utilization of adult stem cells and pluripotent stem cells hold immense potential for replenishing lost cardiomyocytes and facilitating cardiac tissue repair and regeneration. Tissue engineering also plays a prominent role employing synthetic or natural biomaterials, engineering cardiac patches and grafts with suitable properties, and fabricating upscale bioreactors to create functional constructs for cardiac recovery. These constructs can be transplanted into heart to provide mechanical support and facilitate tissue healing. Additionally, the production of organoids and chips that accurately replicate the structure and function of the whole organ is an area of extensive research. Despite significant progress, several challenges persist in the field of cardiac regeneration. These include enhancing cell survival and engraftment, achieving proper vascularization, and ensuring the long-term functionality of engineered constructs. Overcoming these obstacles offering effective therapies to restore cardiac function could improve the quality of life for individuals with heart diseases.
... According to statistical investigations, heart diseases are the leading cause of death worldwide. Both heredity and genetics play important roles in the development of heart diseases [1][2][3][4]. For example, congenital heart disease (CHD) is the most common congenital malformation [5]. ...
... By introducing living cells into these microchips and subjecting them to dynamic flow conditions, mechanical stimuli, and chemical concentration gradients, it becomes possible to replicate pathophysiology and physiology at the organ level. Advances in biofabrication and biosensing have led to an array of microsensors being employed for analyzing and monitoring cells on these platforms [1,36,37]. Many efforts have been made in the last decade to modify HOCs in various aspects to develop the biomimicry of cardiac tissue cultured in HOCs. ...
Cardiovascular diseases are caused by hereditary factors, environmental conditions, and medication-related issues. On the other hand, the cardiotoxicity of drugs should be thoroughly examined before entering the market. In this regard, heart-on-chip (HOC) systems have been developed as a more efficient and cost-effective solution than traditional methods, such as 2D cell culture and animal models. HOCs must replicate the biology, physiology, and pathology of human heart tissue to be considered a reliable platform for heart disease modeling and drug testing. Therefore, many efforts have been made to find the best methods to fabricate different parts of HOCs and to improve the bio-mimicry of the systems in the last decade. Beating HOCs with different platforms have been developed and techniques, such as fabricating pumpless HOCs, have been used to make HOCs more user-friendly systems. Recent HOC platforms have the ability to simultaneously induce and record electrophysiological stimuli. Additionally, systems including both heart and cancer tissue have been developed to investigate tissue-tissue interactions' effect on cardiac tissue response to cancer drugs. In this review, all steps needed to be considered to fabricate a HOC were introduced, including the choice of cellular resources, biomaterials, fabrication techniques, biomarkers, and corresponding biosensors. Moreover, the current HOCs used for modeling cardiac diseases and testing the drugs are discussed. We finally introduced some suggestions for fabricating relatively more user-friendly HOCs and facilitating the commercialization process.
... This technology was fabricated using microfluidic chips, cells/microtissues, microactuators, and microsensors. Microfluidic channels resemble the in vivo interaction of the organ to blood vessels and modulate cellular interaction, microactuators expose the cells to electrical and mechanical stimulation to resemble the heart's natural physiology, and microsensors detect cell status that aids in the functional analysis [43]. Heart-on-chip technology has been used for drug screening platforms for isoproterenol and in a higher-throughput model of 4 MTFs of 12 assessed drugs [41,42]. ...
... Heart-on-chip technology has been used for drug screening platforms for isoproterenol and in a higher-throughput model of 4 MTFs of 12 assessed drugs [41,42]. Heart-on-chip has also been used to assess molecular interaction in an ischemic-reperfusion injury model and analyse pathophysiology in Barth syndrome [43,44]. ...
Purpose
Cardiac tissue engineering opens up opportunities for regenerative therapy in heart diseases. Current technologies improve engineered cardiac tissue characteristics by combining human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) with non-cardiomyocytes, selective biomaterials, and additional growth factors. Animal models are still required to determine cardiac patches’ overall in vivo effect before initiating human trials. Here, we review the current in vivo studies of cardiac patches using hiPSC-CMs.
Methods
We performed a literature search for studies on cardiac patch in vivo application and compared outcomes based on cell engraftment, functional changes, and safety profiles.
Results
Present studies confirm the beneficial results of combining hiPSC-CMs with other cardiac cell lineages and biomaterials. They improved the functional capacity of the heart, showed a reduction in infarct size, and initiated an adaptive inflammatory process through neovascularisation.
Conclusion
The cardiac patch is currently the most effective delivery system, proving safety and improvements in animal models, which are suggested to be the role of the paracrine mechanism. Further studies should focus on honing in vitro patch characteristics to achieve ideal results.
Lay Summary
Cardiac tissue engineering answers the demand for regenerative therapy in heart diseases. Combining human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) with biomaterials and growth factors in cardiac patches improves the heart’s structural and functional characteristics. This delivery system is safe and efficient for delivering many cells and minimising cellular loss in vivo. Rat and porcine models of ischemic and non-ischemic heart diseases demonstrated the benefits of this therapy, which include cell engraftment, reduced infarct size, and increased left ventricular (LV) systolic function, with no reported critical adverse events. These reports sufficiently provide evidence of feasible improvements to proceed towards further trials.
