Recent Advances in Microfluidic-Based Microphysiological Systems

강성민 한국바이오칩학회 2022 BioChip Journal Vol.16 No.1

Microphysiological systems are in vitro tissue and organ models that present unique opportunities across different disciplines, such as biology, medicine, and engineering. These systems are preferred over two-dimensional simplistic cell cultures and animal models with poor translatability. Microphysiological systems can facilitate the understanding of human physiology and pathophysiology by recapitulating specific organ structures and functions. Recent advances in microphysiological systems employ microfluidic technologies to gain deeper insights into more complex in vivo physiological phenomena and mechanisms. More specifically, microfluidic technologies allow the development of more realistic physiological conditions. This review highlights recent advances in microfluidic-based microphysiological systems and comprehensively discusses the relationship between the design and operation of microfluidic systems for mimicking physiological microenvironments. Moreover, several representative examples and their potential biological applications are described and explained in detail. Finally, the review concludes with current perspectives, limitations, and prospects for further improving the microfluidicbased microphysiological systems.

Microphysiological Engineering of Immune Responses in Intestinal Inflammation

Yoko M. Ambrosini,Woojung Shin,Soyoun Min,Hyun Jung Kim 대한면역학회 2020 Immune Network Vol.20 No.2

The epithelial barrier in the gastrointestinal (GI) tract is a protective interface that endures constant exposure to the external environment while maintaining its close contact with the local immune system. Growing evidence has suggested that the intercellular crosstalk in the GI tract contributes to maintaining the homeostasis in coordination with the intestinal microbiome as well as the tissue-specific local immune elements. Thus, it is critical to map the complex crosstalks in the intestinal epithelial-microbiome-immune (EMI) axis to identify a pathological trigger in the development of intestinal inflammation, including inflammatory bowel disease. However, deciphering a specific contributor to the onset of pathophysiological cascades has been considerably hindered by the challenges in current in vivo and in vitro models. Here, we introduce various microphysiological engineering models of human immune responses in the EMI axis under the healthy conditions and gut inflammation. As a prospective model, we highlight how the human “gut inflammation-on-a-chip” can reconstitute the pathophysiological immune responses and contribute to understanding the independent role of inflammatory factors in the EMI axis on the initiation of immune responses under barrier dysfunction. We envision that the microengineered immune models can be useful to build a customizable patient's chip for the advance in precision medicine.

Mimicking the Human Physiology with Microphysiological Systems (MPS)

성종환,구자민,MichaelL,S 한국바이오칩학회 2019 BioChip Journal Vol.13 No.2

Microphysiological systems (MPS), also known as organ-on-a-chip technology, combine cell culture models and microtechnology to mimic tissue microenvironment and provide improved physiological relevance of in vitro model systems. The unique advantage of MPS technology is manifested where multiple organs interact through complex mechanisms. Multi-organ MPS, or body-on-a-chip systems, aim to recapitulate organ interactions and provide a model of the whole body. Combination of the state-of-the-art microtechnology and mathematical modeling platforms to design and interpret multi-organ systems has contributed to the development of novel MPS for testing drugs and modeling diseases. Here, we summarize recent progress in the development of MPS, with emphasis on multi-organ MPS combined with mathematical models.

From microchannels to microphysiological systems: Development of application specific devices

Yu, James,Lim, Jungeun,Choi, MunSeok,Chung, Minhwan,Jeon, Noo Li Elsevier 2018 MICROELECTRONIC ENGINEERING Vol.202 No.-

<P><B>Abstract</B></P> <P>Microphysiological systems are an emerging field of biomimetic technologies which utilize microfluidics to reconstitute tissue functions within an <I>in vitro</I> environment. Microfluidic organ-on-a-chip platforms exist at the intersection of biology and engineering, straddling the forefront of cutting edge biological research, fluidics, and microfabrication technologies to emulate complex <I>in vitro</I> tissue systems within a highly controllable, accessible, and observable, <I>in vitro</I> environment. Although the advance of cell culture technologies from comparatively rudimentary conventional 2D petri dish based cultures to sophisticated 3D tissue engineering may seem futuristic, the microfluidic engineering concepts behind organ-on-a-chip technologies have deep historical roots which span over half a century. In this paper, we will discuss the shortcomings of conventional cell culture and organ modeling platforms which contributed to the demand for <I>in vitro</I> tissue engineering, as well as provide a background in the technological foundations of microfluidics. We will further recount a brief history of microfluidic cell culture, with emphasis on important developments in fabrication practices and methods of engineering biologically relevant microenvironmental conditions, before discussing the present state of organ specific microfluidic platforms and the future directions that the field may take to overcome present challenges.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Organ-on-a-chip technology for nanoparticle research

Kang Shawn,Park Sunghee Estelle,Huh Dan Dongeun 나노기술연구협의회 2021 Nano Convergence Vol.8 No.20

The last two decades have witnessed explosive growth in the field of nanoengineering and nanomedicine. In particular, engineered nanoparticles have garnered great attention due to their potential to enable new capabilities such as controlled and targeted drug delivery for treatment of various diseases. With rapid progress in nanoparticle research, increasing efforts are being made to develop new technologies for in vitro modeling and analysis of the efficacy and safety of nanotherapeutics in human physiological systems. Organ-on-a-chip technology represents the most recent advance in this effort that provides a promising approach to address the limitations of conventional preclinical models. In this paper, we present a concise review of recent studies demonstrating how this emerging technology can be applied to in vitro studies of nanoparticles. The specific focus of this review is to examine the use of organ-on-a-chip models for toxicity and efficacy assessment of nanoparticles used in therapeutic applications. We also discuss challenges and future opportunities for implementing organ-on-a-chip technology for nanoparticle research.

Microphysiological system with continuous analysis of albumin for hepatotoxicity modeling and drug screening

Arun Asif,박성혁,Afaque Manzoor Soomro,Muhammad Asad Ullah Khalid,Abdul Rahim Chattikatikatuveli Salih,강보혜,Faheem Ahmed,김경환,최경현 한국공업화학회 2021 Journal of Industrial and Engineering Chemistry Vol.98 No.-

In microfluidics, the emergingfield of microphysiological systems (MPS) is overcoming the challenge ofphysiological irrelevancy by animal models for drug discovery and development. Liver function iscritically influenced by drugs owing to its role in drug metabolism and detoxification. Human serumalbumin (HSA) is one of the most important secreted biomarkers which indicate normal liver function. Amicrofluidic albumin immunosensor was developed to be integrated with liver-on-a-chip MPS forcontinuous feedback over disease modeling and treatment. A gold-electrode based electrochemicalimmunosensor was established by anti-HSA antibody immobilization. The liver MPS was found to beefficient for live monitoring of disease modelling and drug treatment over the period of 6 days. Thesystem emulated and analyzed real-time toxicity modeling with HSA sensing. The detection limit ofintegrated sensor was 1 mg/ml with successive reproducibility. The proposed sensor was also validatedwith metabolic biomarkers’ assays. Molecular assays supported the sensor monitoring and depicted liverinjury and recovery. The liver MPS with combined albumin sensor chip may be a promising platform tomimic real-time drug assessment.

Advanced Organotypic In Vitro Model Systems for Host–Microbial Coculture

김래현 한국바이오칩학회 2023 BioChip Journal Vol.17 No.2

In vitro model systems have been advanced to recapitulate important physiological features of the target organ in vivo more closely than the conventional cell line cultures on a petri dish. The advanced organotypic model systems can be used as a complementary or alternative tool for various testing and screening. Numerous data from germ-free animal studies and genome sequencings of clinical samples indicate that human microbiota is an essential part of the human body, but current in vitro model systems rarely include them, which can be one of the reasons for the discrepancy in the tissue phenotypes and outcome of therapeutic intervention between in vivo and in vitro tissues. A coculture model system with appropriate microbes and host cells may have great potential to bridge the gap between the in vitro model and the in vivo counterpart. However, successfully integrating two species in one system introduces new variables to consider and poses new challenges to overcome. This review aims to provide perspectives on the important factors that should be considered for developing organotypic bacterial coculture models. Recent advances in various organotypic bacterial coculture models are highlighted. Finally, challenges and opportunities in developing organotypic microbial coculture models are also discussed.

Printing of Cardiac Microphysiological System for Monitoring the Contractile Force of 3D Engineered Heart Tissue Using Carbon-based Conductive Polymer

U. Yong(용의중),D. Kim(김동환),D. G. Hwang(황동규),S. Cho(조성건),H. Nam(남효영),S. Kim(김세진),T. Y. Kim(김태영),U. Jeong(정운룡),K. Kim(김기훈),W. K. Chung(정완균),J. Jang(장진아) Korean Society for Precision Engineering 2021 한국정밀공학회 학술발표대회 논문집 Vol.2021 No.5월

Effect of shear stress on the proximal tubule-on-a-chip for multi-organ microphysiological system

Hyoungseob Kim,Ju-Bi Lee,Kyunghee Kim,성건용 한국공업화학회 2022 Journal of Industrial and Engineering Chemistry Vol.115 No.-

A multi-organ-on-a-chip (MOC) can be used to induce specific diseases and utilize the absorption, distribution,metabolism, and excretion properties of drugs to enable the prediction and analysis of the drugefficacy in the disease. As a first step to realize the MOC, renal proximal tubular epithelial cells (RPTECs)were cultured on a MOC based on gravity flow to evaluate their excretion function by varying shear stresses. Normal shear stress (0.13 dyne/cm2) and 1.5 and 2 times shear stresses were applied, and the cellviability, transepithelial electrical resistance, glucose reabsorption, and permeability were quantitativelycompared. We confirmed the gene expressions of the drug transporters, conducted a pharmacokinetic(PK) test using metformin, and confirmed the diastolic function of the drug, which is one of the mainfunctions of the RPTECs. The results confirmed that the reabsorption and excretion of the RPTEC werewell reproduced and could be adjusted by the shear stress. It is expected that this will be able to playa role in achieving the complete excretion function from the MOC in future new drug development.

Priming nanoparticle-guided diagnostics and therapeutics towards human organs-on-chips microphysiological system

Choi Jin-Ha,Lee Jaewon,Shin Woojung,최정우,Kim Hyun Jung 나노기술연구협의회 2016 Nano Convergence Vol.3 No.24

Nanotechnology and bioengineering have converged over the past decades, by which the application of multi-functional nanoparticles (NPs) has been emerged in clinical and biomedical fields. The NPs primed to detect disease-specific biomarkers or to deliver biopharmaceutical compounds have beena validated in conventional in vitro culture models including two dimensional (2D) cell cultures or 3D organoid models. However, a lack of experimental models that have strong human physiological relevance has hampered accurate validation of the safety and functionality of NPs. Alternatively, biomimetic human “Organs-on-Chips” microphysiological systems have recapitulated the mechanically dynamic 3D tissue interface of human organ microenvironment, in which the transport, cytotoxicity, biocompatibility, and therapeutic efficacy of NPs and their conjugates may be more accurately validated. Finally, integration of NP-guided diagnostic detection and targeted nanotherapeutics in conjunction with human organs-on-chips can provide a novel avenue to accelerate the NP-based drug development process as well as the rapid detection of cellular secretomes associated with pathophysiological processes.