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REVIEW ARTICLE

           Fabrication and Biomedical Applications of

           Heart-on-a-chip


           Qingzhen Yang  1,2,3,4 , Zhanfeng Xiao , Xuemeng Lv , Tingting Zhang *, Han Liu  6
                                                                                 5
                                                              1,2
                                              1,2
           1 The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and
           Technology, Xi’an Jiaotong University, Xi’an, Shaanxi 710049, P.R. China
           2 Bioinspired Engineering and Biomechanics Center (BEBC), Xi’an Jiaotong University, Xi’an, Shaanxi 710049, P.R. China
           3 Micro-/Nano-technology Research Center, State Key Laboratory for Manufacturing Systems Engineering, Xi’an Jiaotong
           University, Xi’an, Shaanxi 710049, P.R. China
           4 Research Institute of Xi’an Jiaotong University, Hangzhou, Zhejiang 311215, P.R. China
           5 College of Mechanical and Electrical Engineering, Shaanxi University of Science and Technology, Xi’an, Shaanxi 710021,
           P.R. China
           6 Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co-constructed by Henan Province
           and Education Ministry of P.R. China, Academy of Chinese Medical Sciences, Henan University of Chinese Medicine,
           Zhengzhou 450016, P.R. China

           Abstract: 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 advantages
           of heart-on-a-chip include the high portability, high throughput, and the capability to mimic microenvironments in vivo. It has
           shown a great potential in disease mechanism study and drug screening. In this paper, we review the recent advances in heart-
           on-a-chip, including the fabrication methods (e.g., 3D bioprinting) and biomedical applications. By analyzing the structure
           of the existing heart-on-a-chip, we proposed that a highly integrated heart-on-a-chip includes four elements: Microfluidic
           chips, cells/microtissues, microactuators to construct the microenvironment, and microsensors for results readout. Finally, the
           current challenges and future directions of heart-on-a-chip are discussed.

           Keywords: Heart-on-a-chip; Microfluidic chip; Disease model; In vitro culture; Drug screening

           *Correspondence to: Tingting Zhang, College of Mechanical and Electrical Engineering, Shaanxi University of Science and Technology, Xi’an,
           Shaanxi 710021, P.R. China; tting.zhang@sust.edu.cn

           Received: April 21, 2021; Accepted: May 25, 2021; Published Online: June 26, 2021
           (This article belongs to the Special Section: Bioprinting of 3D Functional Tissue Constructs)
           Citation: Yang Q, Xiao Z, Lv X, et al., 2021, Fabrication and Biomedical Applications of Heart-on-a-chip. Int J Bioprint,
           7(3):370. http://doi.org/10.18063/ijb.v7i3.370

           1. Introduction                                     (or  normal)  models.  Overall,  animal  model  and  cell
                                                               culture are the two frequently used methods.
           Heart is one of the most important organs in human body.
           It  provides power  for blood  circulation  which  supplies   These two methods have their own advantages
           oxygen and nutrients to organs and removes metabolic   and  limitations.  For  animal  model,  it  is  different
           waste. In recent years, with the change in dietary   with human being in physiological conditions and
                                                                                 [3]
           structure and the increase of life pressure, heart diseases   organ functionalities .  Thus, the results of animal
           have become the leading cause of death worldwide [1,2] . To   experiments may not precisely predict the response
           study the pathogenesis of heart diseases and pursue the   and/or  functionalities  of humans.  In  addition, animal
           effective treatments, it is of need to establish the disease   experiments have other limitations, such as time-

           © 2021 Yang, et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/
           licenses/by/4.0/), permitting distribution and reproduction in any medium, provided the original work is cited.
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