Editorial

3 pages, 134 KiB

Open AccessEditorial

Microfluidics and Organ-on-a-Chip for Disease Modeling and Drug Screening

by Rohollah Nasiri, Yangzhi Zhu and Natan Roberto de Barros

Biosensors 2024, 14(2), 86; https://doi.org/10.3390/bios14020086 - 04 Feb 2024

Viewed by 1350

The convergence of microfluidics and organ-on-a-chip (OoC) technologies has revolutionized our ability to create advanced in vitro models that recapitulate complex physiological processes [...] Full article

(This article belongs to the Special Issue Microfluidics and Organ-on-a-Chip for Disease Modeling and Drug Screening)

Research

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11 pages, 1455 KiB

Open AccessArticle

Metabolic Assessment of Human Induced Pluripotent Stem Cells-Derived Astrocytes and Fetal Primary Astrocytes: Lactate and Glucose Turnover

by Isabelle Matthiesen, Rohollah Nasiri, Alessandra Tamashiro Orrego, Thomas E. Winkler and Anna Herland

Biosensors 2022, 12(10), 839; https://doi.org/10.3390/bios12100839 - 08 Oct 2022

Cited by 3 | Viewed by 2040

Abstract

Astrocytes represent one of the main cell types in the brain and play a crucial role in brain functions, including supplying the energy demand for neurons. Moreover, they are important regulators of metabolite levels. Glucose uptake and lactate production are some of the [...] Read more.

Astrocytes represent one of the main cell types in the brain and play a crucial role in brain functions, including supplying the energy demand for neurons. Moreover, they are important regulators of metabolite levels. Glucose uptake and lactate production are some of the main observable metabolic actions of astrocytes. To gain insight into these processes, it is essential to establish scalable and functional sources for in vitro studies of astrocytes. In this study, we compared the metabolic turnover of glucose and lactate in astrocytes derived from human induced pluripotent stem cell (hiPSC)-derived Astrocytes (hiAstrocytes) as a scalable astrocyte source to human fetal astrocytes (HFAs). Using a user-friendly, commercial flow-based biosensor, we could verify that hiAstrocytes are as glycogenic as their fetal counterparts, but their normalized metabolic turnover is lower. Specifically, under identical culture conditions in a defined media, HFAs have 2.3 times higher levels of lactate production compared to hiAstrocytes. In terms of glucose, HFAs have 2.1 times higher consumption levels than hiAstrocytes at 24 h. Still, as we describe their glycogenic phenotype, our study demonstrates the use of hiAstrocytes and flow-based biosensors for metabolic studies of astrocyte function. Full article

(This article belongs to the Special Issue Microfluidics and Organ-on-a-Chip for Disease Modeling and Drug Screening)

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14 pages, 3342 KiB

Open AccessArticle

Functional Evaluation and Nephrotoxicity Assessment of Human Renal Proximal Tubule Cells on a Chip

by Bolin Jing, Lei Yan, Jiajia Li, Piaopiao Luo, Xiaoni Ai and Pengfei Tu

Biosensors 2022, 12(9), 718; https://doi.org/10.3390/bios12090718 - 03 Sep 2022

Cited by 4 | Viewed by 1986

Abstract

An in vitro human renal proximal tubule model that represents the proper transporter expression and pronounced epithelial polarization is necessary for the accurate prediction of nephrotoxicity. Here, we constructed a high-throughput human renal proximal tubule model based on an integrated biomimetic array chip [...] Read more.

An in vitro human renal proximal tubule model that represents the proper transporter expression and pronounced epithelial polarization is necessary for the accurate prediction of nephrotoxicity. Here, we constructed a high-throughput human renal proximal tubule model based on an integrated biomimetic array chip (iBAC). Primary human renal proximal tubule epithelial cells (hRPTECs) cultured on this microfluidic platform were able to form a tighter barrier, better transporter function and more sensitive nephrotoxicity prediction than those on the static Transwell. Compared with the human immortalized HK2 model, the hRPTECs model on the chip gained improved apical-basolateral polarization, barrier function and transporter expression. Polymyxin B could induce nephrotoxicity not only from the apical of the hRPTECs, but also from the basolateral side on the iBAC. However, other chemotherapeutic agents, such as doxorubicin and sunitinib, only induced nephrotoxicity from the apical surface of the hRPTECs on the iBAC. In summary, our renal proximal tubule model on the chip exhibits improved epithelial polarization and membrane transporter activity, and can be implemented as an effective nephrotoxicity-screening toolkit. Full article

(This article belongs to the Special Issue Microfluidics and Organ-on-a-Chip for Disease Modeling and Drug Screening)

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18 pages, 2032 KiB

Open AccessArticle

3D Bioprinting of Multi-Material Decellularized Liver Matrix Hydrogel at Physiological Temperatures

by Vamakshi Khati, Harisha Ramachandraiah, Falguni Pati, Helene A. Svahn, Giulia Gaudenzi and Aman Russom

Biosensors 2022, 12(7), 521; https://doi.org/10.3390/bios12070521 - 13 Jul 2022

Cited by 19 | Viewed by 4006

Abstract

Bioprinting is an acclaimed technique that allows the scaling of 3D architectures in an organized pattern but suffers from a scarcity of appropriate bioinks. Decellularized extracellular matrix (dECM) from xenogeneic species has garnered support as a biomaterial to promote tissue-specific regeneration and repair. [...] Read more.

Bioprinting is an acclaimed technique that allows the scaling of 3D architectures in an organized pattern but suffers from a scarcity of appropriate bioinks. Decellularized extracellular matrix (dECM) from xenogeneic species has garnered support as a biomaterial to promote tissue-specific regeneration and repair. The prospect of developing dECM-based 3D artificial tissue is impeded by its inherent low mechanical properties. In recent years, 3D bioprinting of dECM-based bioinks modified with additional scaffolds has advanced the development of load-bearing constructs. However, previous attempts using dECM were limited to low-temperature bioprinting, which is not favorable for a longer print duration with cells. Here, we report the development of a multi-material decellularized liver matrix (dLM) bioink reinforced with gelatin and polyethylene glycol to improve rheology, extrudability, and mechanical stability. This shear-thinning bioink facilitated extrusion-based bioprinting at 37 °C with HepG2 cells into a 3D grid structure with a further enhancement for long-term applications by enzymatic crosslinking with mushroom tyrosinase. The heavily crosslinked structure showed a 16-fold increase in viscosity (2.73 Pa s⁻¹) and a 32-fold increase in storage modulus from the non-crosslinked dLM while retaining high cell viability (85–93%) and liver-specific functions. Our results show that the cytocompatible crosslinking of dLM bioink at physiological temperatures has promising applications for extended 3D-printing procedures. Full article

(This article belongs to the Special Issue Microfluidics and Organ-on-a-Chip for Disease Modeling and Drug Screening)

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Review

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28 pages, 28352 KiB

Open AccessReview

Microenvironments Matter: Advances in Brain-on-Chip

by Gulden Akcay and Regina Luttge

Biosensors 2023, 13(5), 551; https://doi.org/10.3390/bios13050551 - 16 May 2023

Cited by 5 | Viewed by 2228

Abstract

To highlight the particular needs with respect to modeling the unique and complex organization of the human brain structure, we reviewed the state-of-the-art in devising brain models with engineered instructive microenvironments. To acquire a better perspective on the brain’s working mechanisms, we first [...] Read more.

To highlight the particular needs with respect to modeling the unique and complex organization of the human brain structure, we reviewed the state-of-the-art in devising brain models with engineered instructive microenvironments. To acquire a better perspective on the brain’s working mechanisms, we first summarize the importance of regional stiffness gradients in brain tissue, varying per layer and the cellular diversities of the layers. Through this, one can acquire an understanding of the essential parameters in emulating the brain in vitro. In addition to the brain’s organizational architecture, we addressed also how the mechanical properties have an impact on neuronal cell responses. In this respect, advanced in vitro platforms emerged and profoundly changed the methods of brain modeling efforts from the past, mainly focusing on animal or cell line research. The main challenges in imitating features of the brain in a dish are with regard to composition and functionality. In neurobiological research, there are now methods that aim to cope with such challenges by the self-assembly of human-derived pluripotent stem cells (hPSCs), i.e., brainoids. Alternatively, these brainoids can be used stand-alone or in conjunction with Brain-on-Chip (BoC) platform technology, 3D-printed gels, and other types of engineered guidance features. Currently, advanced in vitro methods have made a giant leap forward regarding cost-effectiveness, ease-of-use, and availability. We bring these recent developments together into one review. We believe our conclusions will give a novel perspective towards advancing instructive microenvironments for BoCs and the understanding of the brain’s cellular functions either in modeling healthy or diseased states of the brain. Full article

(This article belongs to the Special Issue Microfluidics and Organ-on-a-Chip for Disease Modeling and Drug Screening)

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23 pages, 2138 KiB

Open AccessReview

Microfluidic Gut-on-a-Chip: Fundamentals and Challenges

by Dimple Palanilkunnathil Thomas, Jun Zhang, Nam-Trung Nguyen and Hang Thu Ta

Biosensors 2023, 13(1), 136; https://doi.org/10.3390/bios13010136 - 13 Jan 2023

Cited by 14 | Viewed by 6850

Abstract

The human gut is responsible for food digestion and absorption. Recently, growing evidence has shown its vital role in the proper functioning of other organs. Advances in microfluidic technologies have made a significant impact on the biomedical field. Specifically, organ-on-a-chip technology (OoC), which [...] Read more.

The human gut is responsible for food digestion and absorption. Recently, growing evidence has shown its vital role in the proper functioning of other organs. Advances in microfluidic technologies have made a significant impact on the biomedical field. Specifically, organ-on-a-chip technology (OoC), which has become a popular substitute for animal models, is capable of imitating complex systems in vitro and has been used to study pathology and pharmacology. Over the past decade, reviews published focused more on the applications and prospects of gut-on-a-chip (GOC) technology, but the challenges and solutions to these limitations were often overlooked. In this review, we cover the physiology of the human gut and review the engineering approaches of GOC. Fundamentals of GOC models including materials and fabrication, cell types, stimuli and gut microbiota are thoroughly reviewed. We discuss the present GOC model applications, challenges, possible solutions and prospects for the GOC models and technology. Full article

(This article belongs to the Special Issue Microfluidics and Organ-on-a-Chip for Disease Modeling and Drug Screening)

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32 pages, 4938 KiB

Open AccessReview

Recent Progresses in Development of Biosensors for Thrombin Detection

by Reza Eivazzadeh-Keihan, Zahra Saadatidizaji, Ali Maleki, Miguel de la Guardia, Mohammad Mahdavi, Sajjad Barzegar and Samad Ahadian

Biosensors 2022, 12(9), 767; https://doi.org/10.3390/bios12090767 - 19 Sep 2022

Cited by 15 | Viewed by 3024

Abstract

Thrombin is a serine protease with an essential role in homeostasis and blood coagulation. During vascular injuries, thrombin is generated from prothrombin, a plasma protein, to polymerize fibrinogen molecules into fibrin filaments. Moreover, thrombin is a potent stimulant for platelet activation, which causes [...] Read more.

Thrombin is a serine protease with an essential role in homeostasis and blood coagulation. During vascular injuries, thrombin is generated from prothrombin, a plasma protein, to polymerize fibrinogen molecules into fibrin filaments. Moreover, thrombin is a potent stimulant for platelet activation, which causes blood clots to prevent bleeding. The rapid and sensitive detection of thrombin is important in biological analysis and clinical diagnosis. Hence, various biosensors for thrombin measurement have been developed. Biosensors are devices that produce a quantifiable signal from biological interactions in proportion to the concentration of a target analyte. An aptasensor is a biosensor in which a DNA or RNA aptamer has been used as a biological recognition element and can identify target molecules with a high degree of sensitivity and affinity. Designed biosensors could provide effective methods for the highly selective and specific detection of thrombin. This review has attempted to provide an update of the various biosensors proposed in the literature, which have been designed for thrombin detection. According to their various transducers, the constructions and compositions, the performance, benefits, and restrictions of each are summarized and compared. Full article

(This article belongs to the Special Issue Microfluidics and Organ-on-a-Chip for Disease Modeling and Drug Screening)

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Other

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10 pages, 1013 KiB

Open AccessPerspective

Academic User View: Organ-on-a-Chip Technology

by Mathias Busek, Aleksandra Aizenshtadt, Mikel Amirola-Martinez, Ludivine Delon and Stefan Krauss

Biosensors 2022, 12(2), 126; https://doi.org/10.3390/bios12020126 - 16 Feb 2022

Cited by 16 | Viewed by 4717

Abstract

Organ-on-a-Chip (OoC) systems bring together cell biology, engineering, and material science for creating systems that recapitulate the in vivo microenvironment of tissues and organs. The versatility of OoC systems enables in vitro models for studying physiological processes, drug development, and testing in both [...] Read more.

Organ-on-a-Chip (OoC) systems bring together cell biology, engineering, and material science for creating systems that recapitulate the in vivo microenvironment of tissues and organs. The versatility of OoC systems enables in vitro models for studying physiological processes, drug development, and testing in both academia and industry. This paper evaluates current platforms from the academic end-user perspective, elaborating on usability, complexity, and robustness. We surveyed 187 peers in 35 countries and grouped the responses according to preliminary knowledge and the source of the OoC systems that are used. The survey clearly shows that current commercial OoC platforms provide a substantial level of robustness and usability—which is also indicated by an increasing adaptation of the pharmaceutical industry—but a lack of complexity can challenge their use as a predictive platform. Self-made systems, on the other hand, are less robust and standardized but provide the opportunity to develop customized and more complex models, which are often needed for human disease modeling. This perspective serves as a guide for researchers in the OoC field and encourages the development of next-generation OoCs. Full article

(This article belongs to the Special Issue Microfluidics and Organ-on-a-Chip for Disease Modeling and Drug Screening)

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