Special Issue "Advanced 3D Cell Culture Techniques in Micro-Bioreactors"

A special issue of Processes (ISSN 2227-9717). This special issue belongs to the section "Biological Systems".

Deadline for manuscript submissions: 31 August 2021.

Special Issue Editors

Prof. Dr. Eric Gottwald
E-Mail Website
Guest Editor
Institute of Functional Interfaces, Karlsruhe Institute of Technology, Karlsruhe 76021, Germany
Interests: stem cells; artificial stem cell niches; leukemic and hematopoietic stem cells; 3D-co-culture systems; micro-bioreactor development
Dr. Brigitte Altmann
E-Mail Website
Guest Editor
G.E.R.N. Center for Tissue Replacement, Regeneration and Neogenesis, Department of Prosthetic Dentistry, Medical Center - University of Freiburg, Freiburg 79108, Germany
Interests: 3D cell culture; micro-bioreactors; cell-biomaterial interactions; cell biology-inspired bone regeneration; bone cell differentiation

Special Issue Information

Dear Colleagues,

For more than 100 years, cell cultures have been performed in petri dishes and their derivatives, such as culture flasks or multiwell plates. The establishment of such static 2D cultures for cell-based in vitro studies represents a convenient method for screening purposes and basic research, as they allow the complexity of the in vivo situation, which is characterized by a plethora of cell and tissue interactions, to be circumvented. To get one step closer to the in vivo situation, the in vitro toolbox may be extended by organotypic 3D cultures in micro-bioreactors, which enable the generation of more in-vivo-like results with respect to the cellular microenvironment, namely matrix attachment and a pericellular fluid flow environment. Therefore, 3D cultures in micro-bioreactors represent an additional step during the translational process of in vitro information into the field of tissue engineering, biomaterials, and drug development.

With this Special Issue of Processes, we aim to give an overview of the current developments in 3D culture-based micro-bioreactor systems and their corresponding in vitro models, as well as their potential applications. Topics include, but are not limited to, the following:

  • Transferring 2D-cultures into 3D;
  • Applying an active flow;
  • Combining different cell types for advanced 3D co-culture models;
  • Miniaturization of cultures, e.g., for organ-on-a-chip devices;
  • High-content-/high-throughput-capable micro-bioreactors;
  • Micro-bioreactors in basic research;
  • Micro-bioreactors as test beds in drug development;
  • Micro-bioreactors for personalized medicine applications.

Prof. Dr. Eric Gottwald
Dr. Brigitte Altmann
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Processes is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • 3D cell culture
  • co-culture
  • micro-bioreactor
  • active flow
  • stem cells
  • differentiation
  • drug development
  • primary cell culture
  • organotypic culture

Published Papers (4 papers)

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Research

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Open AccessArticle
Intracellular Sodium Changes in Cancer Cells Using a Microcavity Array-Based Bioreactor System and Sodium Triple-Quantum MR Signal
Processes 2020, 8(10), 1267; https://doi.org/10.3390/pr8101267 - 09 Oct 2020
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Abstract
The sodium triple-quantum (TQ) magnetic resonance (MR) signal created by interactions of sodium ions with macromolecules has been demonstrated to be a valuable biomarker for cell viability. The aim of this study was to monitor a cellular response using the sodium TQ signal [...] Read more.
The sodium triple-quantum (TQ) magnetic resonance (MR) signal created by interactions of sodium ions with macromolecules has been demonstrated to be a valuable biomarker for cell viability. The aim of this study was to monitor a cellular response using the sodium TQ signal during inhibition of Na/K-ATPase in living cancer cells (HepG2). The cells were dynamically investigated after exposure to 1 mM ouabain or K+-free medium for 60 min using an MR-compatible bioreactor system. An improved TQ time proportional phase incrementation (TQTPPI) pulse sequence with almost four times TQ signal-to-noise ratio (SNR) gain allowed for conducting experiments with 12–14 × 106 cells using a 9.4 T MR scanner. During cell intervention experiments, the sodium TQ signal increased to 138.9 ± 4.1% and 183.4 ± 8.9% for 1 mM ouabain (n = 3) and K+-free medium (n = 3), respectively. During reperfusion with normal medium, the sodium TQ signal further increased to 169.2 ± 5.3% for the ouabain experiment, while it recovered to 128.5 ± 6.8% for the K+-free experiment. These sodium TQ signal increases agree with an influx of sodium ions during Na/K-ATPase inhibition and hence a reduced cell viability. The improved TQ signal detection combined with this MR-compatible bioreactor system provides a capability to investigate the cellular response of a variety of cells using the sodium TQ MR signal. Full article
(This article belongs to the Special Issue Advanced 3D Cell Culture Techniques in Micro-Bioreactors)
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Review

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Open AccessFeature PaperReview
Digital Twins for Tissue Culture Techniques—Concepts, Expectations, and State of the Art
Processes 2021, 9(3), 447; https://doi.org/10.3390/pr9030447 - 02 Mar 2021
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Abstract
Techniques to provide in vitro tissue culture have undergone significant changes during the last decades, and current applications involve interactions of cells and organoids, three-dimensional cell co-cultures, and organ/body-on-chip tools. Efficient computer-aided and mathematical model-based methods are required for efficient and knowledge-driven characterization, [...] Read more.
Techniques to provide in vitro tissue culture have undergone significant changes during the last decades, and current applications involve interactions of cells and organoids, three-dimensional cell co-cultures, and organ/body-on-chip tools. Efficient computer-aided and mathematical model-based methods are required for efficient and knowledge-driven characterization, optimization, and routine manufacturing of tissue culture systems. As an alternative to purely experimental-driven research, the usage of comprehensive mathematical models as a virtual in silico representation of the tissue culture, namely a digital twin, can be advantageous. Digital twins include the mechanistic of the biological system in the form of diverse mathematical models, which describe the interaction between tissue culture techniques and cell growth, metabolism, and the quality of the tissue. In this review, current concepts, expectations, and the state of the art of digital twins for tissue culture concepts will be highlighted. In general, DT’s can be applied along the full process chain and along the product life cycle. Due to the complexity, the focus of this review will be especially on the design, characterization, and operation of the tissue culture techniques. Full article
(This article belongs to the Special Issue Advanced 3D Cell Culture Techniques in Micro-Bioreactors)
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Open AccessFeature PaperReview
Advanced 3D Cell Culture Techniques in Micro-Bioreactors, Part II: Systems and Applications
Processes 2021, 9(1), 21; https://doi.org/10.3390/pr9010021 - 23 Dec 2020
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Abstract
In this second part of our systematic review on the research area of 3D cell culture in micro-bioreactors we give a detailed description of the published work with regard to the existing micro-bioreactor types and their applications, and highlight important results gathered with [...] Read more.
In this second part of our systematic review on the research area of 3D cell culture in micro-bioreactors we give a detailed description of the published work with regard to the existing micro-bioreactor types and their applications, and highlight important results gathered with the respective systems. As an interesting detail, we found that micro-bioreactors have already been used in SARS-CoV research prior to the SARS-CoV2 pandemic. As our literature research revealed a variety of 3D cell culture configurations in the examined bioreactor systems, we defined in review part one “complexity levels” by means of the corresponding 3D cell culture techniques applied in the systems. The definition of the complexity is thereby based on the knowledge that the spatial distribution of cell-extracellular matrix interactions and the spatial distribution of homologous and heterologous cell–cell contacts play an important role in modulating cell functions. Because at least one of these parameters can be assigned to the 3D cell culture techniques discussed in the present review, we structured the studies according to the complexity levels applied in the MBR systems. Full article
(This article belongs to the Special Issue Advanced 3D Cell Culture Techniques in Micro-Bioreactors)
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Open AccessFeature PaperReview
Advanced 3D Cell Culture Techniques in Micro-Bioreactors, Part I: A Systematic Analysis of the Literature Published between 2000 and 2020
Processes 2020, 8(12), 1656; https://doi.org/10.3390/pr8121656 - 15 Dec 2020
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Abstract
Bioreactors have proven useful for a vast amount of applications. Besides classical large-scale bioreactors and fermenters for prokaryotic and eukaryotic organisms, micro-bioreactors, as specialized bioreactor systems, have become an invaluable tool for mammalian 3D cell cultures. In this systematic review we analyze the [...] Read more.
Bioreactors have proven useful for a vast amount of applications. Besides classical large-scale bioreactors and fermenters for prokaryotic and eukaryotic organisms, micro-bioreactors, as specialized bioreactor systems, have become an invaluable tool for mammalian 3D cell cultures. In this systematic review we analyze the literature in the field of eukaryotic 3D cell culture in micro-bioreactors within the last 20 years. For this, we define complexity levels with regard to the cellular 3D microenvironment concerning cell–matrix-contact, cell–cell-contact and the number of different cell types present at the same time. Moreover, we examine the data with regard to the micro-bioreactor design including mode of cell stimulation/nutrient supply and materials used for the micro-bioreactors, the corresponding 3D cell culture techniques and the related cellular microenvironment, the cell types and in vitro models used. As a data source we used the National Library of Medicine and analyzed the studies published from 2000 to 2020. Full article
(This article belongs to the Special Issue Advanced 3D Cell Culture Techniques in Micro-Bioreactors)
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