Special Issue "Human Organs-on-Chips for In Vitro Disease Models"

A special issue of Bioengineering (ISSN 2306-5354).

Deadline for manuscript submissions: closed (31 May 2017)

Special Issue Editor

Guest Editor
Dr. Hyun Jung Kim

Department of Biomedical Engineering, The University of Texas at Austin, USA
Website | E-Mail
Interests: human organs-on-chips; human microbiome; host-microbe interaction; microfluidics; synthetic microbial ecosystem; disease mode

Special Issue Information

Dear Colleagues,

The first generation of biomimetic microphysiological systems, so called “Human Organs-on-Chips”, has presented prodigious potential to reconstitute the 3D microarchitecture as well as the mechanical dynamics of human organs. In these engineered microsystem surrogate models, organ-level functions and in vivo relevant physiological responses have been recapitulated wherein the tissue-specific interactions may be in response to chemical (drugs, toxins, nutrients), physical (fluid shear stresses, mechanical deformations), or biological stimulations (microbiome, immune cells) and can be manipulated in a spatiotemporal manner.

With the breakthroughs of human organs-on-chips, the concept of “Biomimetic Reverse Engineering” that selects a minimal set of key pathophysiological factors has provided promising clues not only for the structural and functional reconstitution of human organs, but also for the modular recapitulation of a complex living system. For instance, by leveraging the microphysiological system, we can now decouple the complex pathophysiological factors contributing to diseases, then recouple the key interacting factors involved in the specific disease process.

Here, we envision that the next generation of the human organs-on-chips may rapidly validate the safety and efficacy of drug candidates, precisely dissect the complicated disease development, or faithfully assess the in vivo responses during clinical interventions. We may also contemplate to recruit human patient samples, integrate 3D organoid culture technology, replace synthetic materials with programmable biomaterials, rebuild sophisticated organ microarchitecture via 3D printing technology, or incorporate nanotechnology and bioelectronics-based sensing and detection modules in combination with the organs-on-chips.

We announce the Special Issue “Human Organs-on-Chips for In Vitro Disease Models” to come up with comprehensive understanding of the current state-of-the-art technologies in combination with the human microphysiological systems to emulate human diseases.

We look forward to receiving your contributions for this Special Issue.

Dr. Hyun Jung Kim
Guest Editor

Manuscript Submission Information

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Keywords

  • Human organs-on-chips
  • Microphysiological systems
  • In vitro disease models
  • Human microbiome
  • Biomimetic/bioinspired microengineering
  • 3D organoid cultures
  • Biomaterials
  • Bioelectronics
  • Nano-scale technology
  • 3D printing technology
  • Microfluidics

Published Papers (8 papers)

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Research

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Open AccessArticle Three-Dimensional Culture Model of Skeletal Muscle Tissue with Atrophy Induced by Dexamethasone
Bioengineering 2017, 4(2), 56; doi:10.3390/bioengineering4020056
Received: 12 April 2017 / Revised: 12 June 2017 / Accepted: 12 June 2017 / Published: 15 June 2017
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Abstract
Drug screening systems for muscle atrophy based on the contractile force of cultured skeletal muscle tissues are required for the development of preventive or therapeutic drugs for atrophy. This study aims to develop a muscle atrophy model by inducing atrophy in normal muscle
[...] Read more.
Drug screening systems for muscle atrophy based on the contractile force of cultured skeletal muscle tissues are required for the development of preventive or therapeutic drugs for atrophy. This study aims to develop a muscle atrophy model by inducing atrophy in normal muscle tissues constructed on microdevices capable of measuring the contractile force and to verify if this model is suitable for drug screening using the contractile force as an index. Tissue engineered skeletal muscles containing striated myotubes were prepared on the microdevices for the study. The addition of 100 µM dexamethasone (Dex), which is used as a muscle atrophy inducer, for 24 h reduced the contractile force significantly. An increase in the expression of Atrogin-1 and MuRF-1 in the tissues treated with Dex was established. A decrease in the number of striated myotubes was also observed in the tissues treated with Dex. Treatment with 8 ng/mL Insulin-like Growth Factor (IGF-I) for 24 h significantly increased the contractile force of the Dex-induced atrophic tissues. The same treatment, though, had no impact on the force of the normal tissues. Thus, it is envisaged that the atrophic skeletal muscle tissues induced by Dex can be used for drug screening against atrophy. Full article
(This article belongs to the Special Issue Human Organs-on-Chips for In Vitro Disease Models)
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Review

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Open AccessReview Microdevice Platform for In Vitro Nervous System and Its Disease Model
Bioengineering 2017, 4(3), 77; doi:10.3390/bioengineering4030077
Received: 7 June 2017 / Revised: 7 September 2017 / Accepted: 7 September 2017 / Published: 13 September 2017
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Abstract
The development of precise microdevices can be applied to the reconstruction of in vitro human microenvironmental systems with biomimetic physiological conditions that have highly tunable spatial and temporal features. Organ-on-a-chip can emulate human physiological functions, particularly at the organ level, as well as
[...] Read more.
The development of precise microdevices can be applied to the reconstruction of in vitro human microenvironmental systems with biomimetic physiological conditions that have highly tunable spatial and temporal features. Organ-on-a-chip can emulate human physiological functions, particularly at the organ level, as well as its specific roles in the body. Due to the complexity of the structure of the central nervous system and its intercellular interaction, there remains an urgent need for the development of human brain or nervous system models. Thus, various microdevice models have been proposed to mimic actual human brain physiology, which can be categorized as nervous system-on-a-chip. Nervous system-on-a-chip platforms can prove to be promising technologies, through the application of their biomimetic features to the etiology of neurodegenerative diseases. This article reviews the microdevices for nervous system-on-a-chip platform incorporated with neurobiology and microtechnology, including microfluidic designs that are biomimetic to the entire nervous system. The emulation of both neurodegenerative disorders and neural stem cell behavior patterns in micro-platforms is also provided, which can be used as a basis to construct nervous system-on-a-chip. Full article
(This article belongs to the Special Issue Human Organs-on-Chips for In Vitro Disease Models)
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Open AccessReview 3D Bioprinting and In Vitro Cardiovascular Tissue Modeling
Bioengineering 2017, 4(3), 71; doi:10.3390/bioengineering4030071
Received: 26 June 2017 / Revised: 10 August 2017 / Accepted: 11 August 2017 / Published: 18 August 2017
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Abstract
Numerous microfabrication approaches have been developed to recapitulate morphologically and functionally organized tissue microarchitectures in vitro; however, the technical and operational limitations remain to be overcome. 3D printing technology facilitates the building of a construct containing biomaterials and cells in desired organizations and
[...] Read more.
Numerous microfabrication approaches have been developed to recapitulate morphologically and functionally organized tissue microarchitectures in vitro; however, the technical and operational limitations remain to be overcome. 3D printing technology facilitates the building of a construct containing biomaterials and cells in desired organizations and shapes that have physiologically relevant geometry, complexity, and micro-environmental cues. The selection of biomaterials for 3D printing is considered one of the most critical factors to achieve tissue function. It has been reported that some printable biomaterials, having extracellular matrix-like intrinsic microenvironment factors, were capable of regulating stem cell fate and phenotype. In particular, this technology can control the spatial positions of cells, and provide topological, chemical, and complex cues, allowing neovascularization and maturation in the engineered cardiovascular tissues. This review will delineate the state-of-the-art 3D bioprinting techniques in the field of cardiovascular tissue engineering and their applications in translational medicine. In addition, this review will describe 3D printing-based pre-vascularization technologies correlated with implementing blood perfusion throughout the engineered tissue equivalent. The described engineering method may offer a unique approach that results in the physiological mimicry of human cardiovascular tissues to aid in drug development and therapeutic approaches. Full article
(This article belongs to the Special Issue Human Organs-on-Chips for In Vitro Disease Models)
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Open AccessReview Tumor Microenvironment on a Chip: The Progress and Future Perspective
Bioengineering 2017, 4(3), 64; doi:10.3390/bioengineering4030064
Received: 27 May 2017 / Revised: 17 July 2017 / Accepted: 19 July 2017 / Published: 21 July 2017
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Abstract
Tumors develop in intricate microenvironments required for their sustained growth, invasion, and metastasis. The tumor microenvironment plays a critical role in the malignant or drug resistant nature of tumors, becoming a promising therapeutic target. Microengineered physiological systems capable of mimicking tumor environments are
[...] Read more.
Tumors develop in intricate microenvironments required for their sustained growth, invasion, and metastasis. The tumor microenvironment plays a critical role in the malignant or drug resistant nature of tumors, becoming a promising therapeutic target. Microengineered physiological systems capable of mimicking tumor environments are one emerging platform that allows for quantitative and reproducible characterization of tumor responses with pathophysiological relevance. This review highlights the recent advancements of engineered tumor microenvironment systems that enable the unprecedented mechanistic examination of cancer progression and metastasis. We discuss the progress and future perspective of these microengineered biomimetic approaches for anticancer drug prescreening applications. Full article
(This article belongs to the Special Issue Human Organs-on-Chips for In Vitro Disease Models)
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Open AccessReview Microtechnology-Based Multi-Organ Models
Bioengineering 2017, 4(2), 46; doi:10.3390/bioengineering4020046
Received: 19 March 2017 / Revised: 17 May 2017 / Accepted: 18 May 2017 / Published: 21 May 2017
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Abstract
Drugs affect the human body through absorption, distribution, metabolism, and elimination (ADME) processes. Due to their importance, the ADME processes need to be studied to determine the efficacy and side effects of drugs. Various in vitro model systems have been developed and used
[...] Read more.
Drugs affect the human body through absorption, distribution, metabolism, and elimination (ADME) processes. Due to their importance, the ADME processes need to be studied to determine the efficacy and side effects of drugs. Various in vitro model systems have been developed and used to realize the ADME processes. However, conventional model systems have failed to simulate the ADME processes because they are different from in vivo, which has resulted in a high attrition rate of drugs and a decrease in the productivity of new drug development. Recently, a microtechnology-based in vitro system called “organ-on-a-chip” has been gaining attention, with more realistic cell behavior and physiological reactions, capable of better simulating the in vivo environment. Furthermore, multi-organ-on-a-chip models that can provide information on the interaction between the organs have been developed. The ultimate goal is the development of a “body-on-a-chip”, which can act as a whole body model. In this review, we introduce and summarize the current progress in the development of multi-organ models as a foundation for the development of body-on-a-chip. Full article
(This article belongs to the Special Issue Human Organs-on-Chips for In Vitro Disease Models)
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Open AccessReview The Role of Microfluidics for Organ on Chip Simulations
Bioengineering 2017, 4(2), 39; doi:10.3390/bioengineering4020039
Received: 24 March 2017 / Revised: 1 May 2017 / Accepted: 2 May 2017 / Published: 4 May 2017
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Abstract
A multichannel three-dimensional chip of a microfluidic cell culture which enables the simulation of organs is called an “organ on a chip” (OC). With the integration of many other technologies, OCs have been mimicking organs, substituting animal models, and diminishing the time and
[...] Read more.
A multichannel three-dimensional chip of a microfluidic cell culture which enables the simulation of organs is called an “organ on a chip” (OC). With the integration of many other technologies, OCs have been mimicking organs, substituting animal models, and diminishing the time and cost of experiments which is better than the preceding conventional in vitro models, which make them imperative tools for finding functional properties, pathological states, and developmental studies of organs. In this review, recent progress regarding microfluidic devices and their applications in cell cultures is discussed to explain the advantages and limitations of these systems. Microfluidics is not a solution but only an approach to create a controlled environment, however, other supporting technologies are needed, depending upon what is intended to be achieved. Microfluidic platforms can be integrated with additional technologies to enhance the organ on chip simulations. Besides, new directions and areas are mentioned for interested researchers in this field, and future challenges regarding the simulation of OCs are also discussed, which will make microfluidics more accurate and beneficial for biological applications. Full article
(This article belongs to the Special Issue Human Organs-on-Chips for In Vitro Disease Models)
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Open AccessReview 3D Printing of Organs-On-Chips
Bioengineering 2017, 4(1), 10; doi:10.3390/bioengineering4010010
Received: 29 November 2016 / Revised: 14 January 2017 / Accepted: 20 January 2017 / Published: 25 January 2017
Cited by 4 | PDF Full-text (2452 KB) | HTML Full-text | XML Full-text
Abstract
Organ-on-a-chip engineering aims to create artificial living organs that mimic the complex and physiological responses of real organs, in order to test drugs by precisely manipulating the cells and their microenvironments. To achieve this, the artificial organs should to be microfabricated with an
[...] Read more.
Organ-on-a-chip engineering aims to create artificial living organs that mimic the complex and physiological responses of real organs, in order to test drugs by precisely manipulating the cells and their microenvironments. To achieve this, the artificial organs should to be microfabricated with an extracellular matrix (ECM) and various types of cells, and should recapitulate morphogenesis, cell differentiation, and functions according to the native organ. A promising strategy is 3D printing, which precisely controls the spatial distribution and layer-by-layer assembly of cells, ECMs, and other biomaterials. Owing to this unique advantage, integration of 3D printing into organ-on-a-chip engineering can facilitate the creation of micro-organs with heterogeneity, a desired 3D cellular arrangement, tissue-specific functions, or even cyclic movement within a microfluidic device. Moreover, fully 3D-printed organs-on-chips more easily incorporate other mechanical and electrical components with the chips, and can be commercialized via automated massive production. Herein, we discuss the recent advances and the potential of 3D cell-printing technology in engineering organs-on-chips, and provides the future perspectives of this technology to establish the highly reliable and useful drug-screening platforms. Full article
(This article belongs to the Special Issue Human Organs-on-Chips for In Vitro Disease Models)
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Open AccessReview Vasculature-On-A-Chip for In Vitro Disease Models
Bioengineering 2017, 4(1), 8; doi:10.3390/bioengineering4010008
Received: 29 November 2016 / Revised: 17 January 2017 / Accepted: 19 January 2017 / Published: 24 January 2017
Cited by 1 | PDF Full-text (1665 KB) | HTML Full-text | XML Full-text
Abstract
Vascularization, the formation of new blood vessels, is an essential biological process. As the vasculature is involved in various fundamental physiological phenomena and closely related to several human diseases, it is imperative that substantial research is conducted on characterizing the vasculature and its
[...] Read more.
Vascularization, the formation of new blood vessels, is an essential biological process. As the vasculature is involved in various fundamental physiological phenomena and closely related to several human diseases, it is imperative that substantial research is conducted on characterizing the vasculature and its related diseases. A significant evolution has been made to describe the vascularization process so that in vitro recapitulation of vascularization is possible. The current microfluidic systems allow elaborative research on the effects of various cues for vascularization, and furthermore, in vitro technologies have a great potential for being applied to the vascular disease models for studying pathological events and developing drug screening platforms. Here, we review methods of fabrication for microfluidic assays and inducing factors for vascularization. We also discuss applications using engineered vasculature such as in vitro vascular disease models, vasculature in organ-on-chips and drug screening platforms. Full article
(This article belongs to the Special Issue Human Organs-on-Chips for In Vitro Disease Models)
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Title: A biomimetic model of tumor-macrophage interactions
Authors: Hunter Joyce, Adán Rodriguez, Amy Brock
Affiliation: Department of Biomedical Engineering, The University of Texas at Austin
Abstract: Reciprocal signaling between tumor cells and their complex microenvironment is a critical determinant of disease progression. Here we develop a spheroid co-culture system to model the in vivo interaction of macrophage cells with mammary tumor cell populations. Analysis of mammary tumors derived from a progressive series of genetically-matched C3-SV40-TAg cancer cell lines revealed differential recruitment of macrophage. Cells derived from a metastatic tumors (C3-SV40-TAg M6C) recruited significantly fewer macrophage than tumor cells derived from a mammary carcinoma (C3-SV40-TAg M6) or from hyperplastic mammary tissue (C3-SV40-TAg M28). Conventional 2D co-culture of the same tumor cells with macrophage failed to mimic the differential recognition and engulfment of the cell line panel. However, co-culture in an alginate gel system revealed differential macrophage engulfment, mimicking the interactions observed in vivo.

Title: Tumor Microenvironment on Chip: The Progress and Future Perspective
Authors: Jungho Ahna,b,Yoshitaka Seia,e, Noo Li Jeonb and YongTae Kima,c,d,e
Affiliation: a George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, USA; b School of Mechanical and Aerospace Engineering, Seoul National University, Seoul, 151-744, Korea; c Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Atlanta, GA, USA; d Institute for Electronics and Nanotechnology, Georgia Institute of Technology, Atlanta, Atlanta, GA, USA; e Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA
Abstract: Tumors develop in intricate microenvironments required for their sustained growth, invasion, and metastasis. The malignant or drug resistant nature of tumors relies on their environments, which become a promising therapeutic target for translational approaches. Microengineered systems mimicking tumor environments are one promising platform to allow quantitative and reproducible characterization of tumor responses in physiologically relevant conditions. This review highlights the recent advancements of microengineered tumor environment systems that enable unprecedented studies on cancer progression and metastasis. We also discuss the progress and future perspective of these microengineered biomimetic approaches for anticancer drug screening applications.

 

 

 

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