Special Issue "Advanced Dynamic Cell and Tissue Culture"

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

Deadline for manuscript submissions: closed (30 April 2018)

Special Issue Editors

Guest Editor
Prof. Dr. Cornelia Kasper

Department of Biotechnology, University of Natural Resources and Life Sciences, Austria
Website | E-Mail
Interests: 3D Cell Culture; Bioreactors; Tissue Engineering; Biomaterials; Stem Cells; Cell Expansion and Differentiation; Dynamic Cultivation; Microfluidics; Automation
Guest Editor
Dr.-Ing. Jan Hansmann

Head of Junior Research Group “Electronic-Tissue Interfaces”, Chair of Tissue Engineering and Regenerative Medicine, University Hospital Wuerzburg, Roentgenring 11, 97070 Wuerzburg
Website | E-Mail

Special Issue Information

Dear Colleagues,

“Classical” standard cell cultivation is still performed under static conditions on 2 D plastic surfaces in ambient atmosphere. These conditions do not mimic physiological in vivo conditions for human primary cells including stem and progenitor cells. For improving cell culture conditions and thus functionality of cells and tissues the expansion and differentiation should be performed in scalable bioreactors in/or on 3 D scaffolds under dynamic conditions. These bioreactor based bioprocesses can be automated and controlled resulting in optimized transport of nutrients and metabolic waste as well as in monitoring and control of the tissue microenvironment.

The current Special Issue wants to highlight new strategies for the development of bioprocesses for organ specific cell cultivation as well as stem cell expansion and differentiation. New designs for 3 D cell culture approaches including co-cultures and scalable systems shall be presented and applications are welcome from the whole field of cell based therapies and in vitro tests. This issue is open for papers addressing:

  • 3 D biomaterials for cell and tissue culture
  • Bioreactor design and optimization including automation
  • Microfluidics (e.g. organ on a chip)
  • Stem cell expansion and differentiation including tissue engineering approaches
  • Application of physiological conditions including mechanical stimulation
  • Sensors and monitoring devices in 3 D cell cultures

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

Prof. Dr. Cornelia Kasper
Dr. .-Ing. Jan Hansmann
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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. Bioengineering is an international peer-reviewed open access quarterly 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 300 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

  • Bioreactors
  • 3 D Cell Culture
  • Tissue Engineering
  • Microfluidics / Organ on a chip
  • Stem Cells
  • Biomaterials
  • Automation

Published Papers (7 papers)

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Editorial

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Open AccessEditorial Advanced Dynamic Cell and Tissue Culture
Bioengineering 2018, 5(3), 65; https://doi.org/10.3390/bioengineering5030065
Received: 3 August 2018 / Accepted: 9 August 2018 / Published: 11 August 2018
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(This article belongs to the Special Issue Advanced Dynamic Cell and Tissue Culture)

Research

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Open AccessArticle Gelatin-Methacryloyl (GelMA) Hydrogels with Defined Degree of Functionalization as a Versatile Toolkit for 3D Cell Culture and Extrusion Bioprinting
Bioengineering 2018, 5(3), 55; https://doi.org/10.3390/bioengineering5030055
Received: 30 May 2018 / Revised: 9 July 2018 / Accepted: 11 July 2018 / Published: 18 July 2018
Cited by 1 | PDF Full-text (8279 KB) | HTML Full-text | XML Full-text
Abstract
Gelatin-methacryloyl (GelMA) is a semi-synthetic hydrogel which consists of gelatin derivatized with methacrylamide and methacrylate groups. These hydrogels provide cells with an optimal biological environment (e.g., RGD motifs for adhesion) and can be quickly photo-crosslinked, which provides shape fidelity and stability at physiological
[...] Read more.
Gelatin-methacryloyl (GelMA) is a semi-synthetic hydrogel which consists of gelatin derivatized with methacrylamide and methacrylate groups. These hydrogels provide cells with an optimal biological environment (e.g., RGD motifs for adhesion) and can be quickly photo-crosslinked, which provides shape fidelity and stability at physiological temperature. In the present work, we demonstrated how GelMA hydrogels can be synthesized with a specific degree of functionalization (DoF) and adjusted to the intended application as a three-dimensional (3D) cell culture platform. The focus of this work lays on producing hydrogel scaffolds which provide a cell promoting microenvironment for human adipose tissue-derived mesenchymal stem cells (hAD-MSCs) and are conductive to their adhesion, spreading, and proliferation. The control of mechanical GelMA properties by variation of concentration, DoF, and ultraviolet (UV) polymerization conditions is described. Moreover, hAD-MSC cell viability and morphology in GelMA of different stiffness was evaluated and compared. Polymerized hydrogels with and without cells could be digested in order to release encapsulated cells without loss of viability. We also demonstrated how hydrogel viscosity can be increased by the use of biocompatible additives, in order to enable the extrusion bioprinting of these materials. Taken together, we demonstrated how GelMA hydrogels can be used as a versatile tool for 3D cell cultivation. Full article
(This article belongs to the Special Issue Advanced Dynamic Cell and Tissue Culture)
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Open AccessArticle 3D Cell Migration Studies for Chemotaxis on Microfluidic-Based Chips: A Comparison between Cardiac and Dermal Fibroblasts
Bioengineering 2018, 5(2), 45; https://doi.org/10.3390/bioengineering5020045
Received: 26 April 2018 / Revised: 7 June 2018 / Accepted: 9 June 2018 / Published: 12 June 2018
Cited by 1 | PDF Full-text (1992 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Fibroblast migration to damaged zones in different tissues is crucial to regenerate and recuperate their functional activity. However, fibroblast migration patterns have hardly been studied in disease terms. Here, we study this fundamental process in dermal and cardiac fibroblasts by means of microfluidic-based
[...] Read more.
Fibroblast migration to damaged zones in different tissues is crucial to regenerate and recuperate their functional activity. However, fibroblast migration patterns have hardly been studied in disease terms. Here, we study this fundamental process in dermal and cardiac fibroblasts by means of microfluidic-based experiments, which simulate a three-dimensional matrix in which fibroblasts are found in physiological conditions. Cardiac fibroblasts show a higher mean and effective speed, as well as greater contractile force, in comparison to dermal fibroblasts. In addition, we generate chemical gradients to study fibroblast response to platelet derived growth factor (PDGF) and transforming growth factor beta (TGF-β) gradients. Dermal fibroblasts were attracted to PDGF, whereas cardiac fibroblasts are not. Notwithstanding, cardiac fibroblasts increased their mean and effective velocity in the presence of TGF-β. Therefore, given that we observe that the application of these growth factors does not modify fibroblasts’ morphology, these alterations in the migration patterns may be due to an intracellular regulation. Full article
(This article belongs to the Special Issue Advanced Dynamic Cell and Tissue Culture)
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Open AccessArticle Bioengineering of a Full-Thickness Skin Equivalent in a 96-Well Insert Format for Substance Permeation Studies and Organ-On-A-Chip Applications
Bioengineering 2018, 5(2), 43; https://doi.org/10.3390/bioengineering5020043
Received: 4 May 2018 / Revised: 30 May 2018 / Accepted: 1 June 2018 / Published: 7 June 2018
Cited by 1 | PDF Full-text (6195 KB) | HTML Full-text | XML Full-text
Abstract
The human skin is involved in protecting the inner body from constant exposure to outer environmental stimuli. There is an evident need to screen for toxicity and the efficacy of drugs and cosmetics applied to the skin. To date, animal studies are still
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The human skin is involved in protecting the inner body from constant exposure to outer environmental stimuli. There is an evident need to screen for toxicity and the efficacy of drugs and cosmetics applied to the skin. To date, animal studies are still the standard method for substance testing, although they are currently controversially discussed Therefore, the multi-organ chip is an attractive alternative to replace animal testing. The two-organ chip is designed to hold 96-well cell culture inserts (CCIs). Small-sized skin equivalents are needed for this. In this study, full-thickness skin equivalents (ftSEs) were generated successfully inside 96-well CCIs. These skin equivalents developed with in vivo-like histological architecture, with normal differentiation marker expressions and proliferation rates. The 96-well CCI-based ftSEs were successfully integrated into the two-organ chip. The permeation of fluorescein sodium salt through the ftSEs was monitored during the culture. The results show a decreasing value for the permeation over time, which seems a promising method to track the development of the ftSEs. Additionally, the permeation was implemented in a computational fluid dynamics simulation, as a tool to predict results in long-term experiments. The advantage of these ftSEs is the reduced need for cells and substances, which makes them more suitable for high throughput assays. Full article
(This article belongs to the Special Issue Advanced Dynamic Cell and Tissue Culture)
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Review

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Open AccessReview Trinity of Three-Dimensional (3D) Scaffold, Vibration, and 3D Printing on Cell Culture Application: A Systematic Review and Indicating Future Direction
Bioengineering 2018, 5(3), 57; https://doi.org/10.3390/bioengineering5030057
Received: 31 May 2018 / Revised: 14 July 2018 / Accepted: 16 July 2018 / Published: 23 July 2018
Cited by 1 | PDF Full-text (1375 KB) | HTML Full-text | XML Full-text
Abstract
Cell culture and cell scaffold engineering have previously developed in two directions. First can be ‘static into dynamic’, with proven effects that dynamic cultures have benefits over static ones. Researches in this direction have used several mechanical means, like external vibrators or shakers,
[...] Read more.
Cell culture and cell scaffold engineering have previously developed in two directions. First can be ‘static into dynamic’, with proven effects that dynamic cultures have benefits over static ones. Researches in this direction have used several mechanical means, like external vibrators or shakers, to approximate the dynamic environments in real tissue, though such approaches could only partly address the issue. Second, can be ‘2D into 3D’, that is, artificially created three-dimensional (3D) passive (also called ‘static’) scaffolds have been utilized for 3D cell culture, helping external culturing conditions mimic real tissue 3D environments in a better way as compared with traditional two-dimensional (2D) culturing. In terms of the fabrication of 3D scaffolds, 3D printing (3DP) has witnessed its high popularity in recent years with ascending applicability, and this tendency might continue to grow along with the rapid development in scaffold engineering. In this review, we first introduce cell culturing, then focus 3D cell culture scaffold, vibration stimulation for dynamic culture, and 3DP technologies fabricating 3D scaffold. Potential interconnection of these realms will be analyzed, as well as the limitations of current 3D scaffold and vibration mechanisms. In the recommendation part, further discussion on future scaffold engineering regarding 3D vibratory scaffold will be addressed, indicating 3DP as a positive bridging technology for future scaffold with integrated and localized vibratory functions. Full article
(This article belongs to the Special Issue Advanced Dynamic Cell and Tissue Culture)
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Open AccessReview Towards Multi-Organoid Systems for Drug Screening Applications
Bioengineering 2018, 5(3), 49; https://doi.org/10.3390/bioengineering5030049
Received: 14 May 2018 / Revised: 15 June 2018 / Accepted: 19 June 2018 / Published: 21 June 2018
Cited by 1 | PDF Full-text (1298 KB) | HTML Full-text | XML Full-text
Abstract
A low percentage of novel drug candidates succeed and reach the end of the drug discovery pipeline, mainly due to poor initial screening and assessment of the effects of the drug and its metabolites over various tissues in the human body. For that,
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A low percentage of novel drug candidates succeed and reach the end of the drug discovery pipeline, mainly due to poor initial screening and assessment of the effects of the drug and its metabolites over various tissues in the human body. For that, emerging technologies involving the production of organoids from human pluripotent stem cells (hPSCs) and the use of organ-on-a-chip devices are showing great promise for developing a more reliable, rapid and cost-effective drug discovery process when compared with the current use of animal models. In particular, the possibility of virtually obtaining any type of cell within the human body, in combination with the ability to create patient-specific tissues using human induced pluripotent stem cells (hiPSCs), broadens the horizons in the fields of drug discovery and personalized medicine. In this review, we address the current progress and challenges related to the process of obtaining organoids from different cell lineages emerging from hPSCs, as well as how to create devices that will allow a precise examination of the in vitro effects generated by potential drugs in different organ systems. Full article
(This article belongs to the Special Issue Advanced Dynamic Cell and Tissue Culture)
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Open AccessReview Dynamic Cultivation of Mesenchymal Stem Cell Aggregates
Bioengineering 2018, 5(2), 48; https://doi.org/10.3390/bioengineering5020048
Received: 2 May 2018 / Revised: 24 May 2018 / Accepted: 15 June 2018 / Published: 19 June 2018
Cited by 1 | PDF Full-text (997 KB) | HTML Full-text | XML Full-text
Abstract
Mesenchymal stem cells (MSCs) are considered as primary candidates for cell-based therapies due to their multiple effects in regenerative medicine. Pre-conditioning of MSCs under physiological conditions—such as hypoxia, three-dimensional environments, and dynamic cultivation—prior to transplantation proved to optimize their therapeutic efficiency. When cultivated
[...] Read more.
Mesenchymal stem cells (MSCs) are considered as primary candidates for cell-based therapies due to their multiple effects in regenerative medicine. Pre-conditioning of MSCs under physiological conditions—such as hypoxia, three-dimensional environments, and dynamic cultivation—prior to transplantation proved to optimize their therapeutic efficiency. When cultivated as three-dimensional aggregates or spheroids, MSCs display increased angiogenic, anti-inflammatory, and immunomodulatory effects as well as improved stemness and survival rates after transplantation, and cultivation under dynamic conditions can increase their viability, proliferation, and paracrine effects, alike. Only few studies reported to date, however, have utilized dynamic conditions for three-dimensional aggregate cultivation of MSCs. Still, the integration of dynamic bioreactor systems, such as spinner flasks or stirred tank reactors might pave the way for a robust, scalable bulk expansion of MSC aggregates or MSC-derived extracellular vesicles. This review summarizes recent insights into the therapeutic potential of MSC aggregate cultivation and focuses on dynamic generation and cultivation techniques of MSC aggregates. Full article
(This article belongs to the Special Issue Advanced Dynamic Cell and Tissue Culture)
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