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Micromachines
Special Issues
Microengineering Techniques for Disease Modeling and Drug Discovery
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Microengineering Techniques for Disease Modeling and Drug Discovery

A special issue of Micromachines (ISSN 2072-666X). This special issue belongs to the section "B：Biology and Biomedicine".

Deadline for manuscript submissions: closed (20 November 2019) | Viewed by 27699

Special Issue Editors

Dr. Mohsen Akbari

E-Mail Website
Guest Editor
Laboratory for Innovations in Microengineering (LiME), Department of Mechanical Engineering, University of Victoria, Victoria, BC V9P 0C8, Canada
Interests: biomaterials; tissue engineering; microfluidics; organs-on-chip; bioprinting; drug delivery; gels
Special Issues, Collections and Topics in MDPI journals
Dr. Carlos Escobedo

E-Mail Website
Guest Editor
Department of Chemical Engineering, Queen’s University, Kingston, ON K7L 3N6, Canada
Interests: microfluidics; bioMEMS; biosensing; lab-on-chip; single cell studies
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Microengineering approaches are enabling technologies for creating biomimetic cell culture systems that recapitulate the cell-cell and cell-tissue interactions, as well as, spatiotemporal chemical gradients, and dynamic mechanical microenvironments in living organs. These bioengineered systems offer unique opportunities for disease modeling and drug discovery due to their ability to promote cellular and tissue organizations which were not possible in conventional monolayer culture systems. The current Special Issue aims to address recent advances in the fabrication and operation of microengineered tissue culture platforms with particular emphasis on microfabricated tissues, single- or multi-organ-on-chip devices, 3D bioprinted tissue models, and multicellular spheroids. The interface of these systems with genomics, metabolomics, and proteomics for the better understanding of disease formation and progression is also of great interest. Moreover, we encourage manuscripts on the development of sensors for long-term monitoring of cellular microenvironments and studies reporting high-throughput designs for investigating the toxicity of drugs and their metabolites.

Dr. Mohsen Akbari
Dr. Carlos Escobedo
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 submissions that pass pre-check are 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. Micromachines 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 2600 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

  • Microfabrication
  • Microengineering
  • Disease Modeling
  • Tissue Engineering
  • Drug discovery
  • Organs-on-chip

Published Papers (5 papers)

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Research

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19 pages, 4644 KiB  
Article
An Engineered Infected Epidermis Model for In Vitro Study of the Skin’s Pro-Inflammatory Response
by Maryam Jahanshahi, David Hamdi, Brent Godau, Ehsan Samiei, Carla Liria Sanchez-Lafuente, Katie J. Neale, Zhina Hadisi, Seyed Mohammad Hossein Dabiri, Erik Pagan, Brian R. Christie and Mohsen Akbari
Micromachines 2020, 11(2), 227; https://doi.org/10.3390/mi11020227 - 23 Feb 2020
Cited by 17 | Viewed by 6826
Abstract
Wound infection is a major clinical challenge that can significantly delay the healing process, can create pain, and requires prolonged hospital stays. Pre-clinical research to evaluate new drugs normally involves animals. However, ethical concerns, cost, and the challenges associated with interspecies variation remain [...] Read more.
Wound infection is a major clinical challenge that can significantly delay the healing process, can create pain, and requires prolonged hospital stays. Pre-clinical research to evaluate new drugs normally involves animals. However, ethical concerns, cost, and the challenges associated with interspecies variation remain major obstacles. Tissue engineering enables the development of in vitro human skin models for drug testing. However, existing engineered skin models are representative of healthy human skin and its normal functions. This paper presents a functional infected epidermis model that consists of a multilayer epidermis structure formed at an air-liquid interface on a hydrogel matrix and a three-dimensionally (3D) printed vascular-like network. The function of the engineered epidermis is evaluated by the expression of the terminal differentiation marker, filaggrin, and the barrier function of the epidermis model using the electrical resistance and permeability across the epidermal layer. The results showed that the multilayer structure enhances the electrical resistance by 40% and decreased the drug permeation by 16.9% in the epidermis model compared to the monolayer cell culture on gelatin. We infect the model with Escherichia coli to study the inflammatory response of keratinocytes by measuring the expression level of pro-inflammatory cytokines (interleukin 1 beta and tumor necrosis factor alpha). After 24 h of exposure to Escherichia coli, the level of IL-1β and TNF-α in control samples were 125 ± 78 and 920 ± 187 pg/mL respectively, while in infected samples, they were 1429 ± 101 and 2155.5 ± 279 pg/mL respectively. However, in ciprofloxacin-treated samples the levels of IL-1β and TNF-α without significant difference with respect to the control reached to 246 ± 87 and 1141.5 ± 97 pg/mL respectively. The robust fabrication procedure and functionality of this model suggest that the model has great potential for modeling wound infections and drug testing. Full article
(This article belongs to the Special Issue Microengineering Techniques for Disease Modeling and Drug Discovery)
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14 pages, 5132 KiB  
Article
A Modular, Reconfigurable Microfabricated Assembly Platform for Microfluidic Transport and Multitype Cell Culture and Drug Testing
by Xin Xie, Sushila Maharjan, Sanwei Liu, Yu Shrike Zhang and Carol Livermore
Micromachines 2020, 11(1), 2; https://doi.org/10.3390/mi11010002 - 18 Dec 2019
Cited by 9 | Viewed by 3503
Abstract
Modular microfluidics offer the opportunity to combine the precise fluid control, rapid sample processing, low sample and reagent volumes, and relatively lower cost of conventional microfluidics with the flexible reconfigurability needed to accommodate the requirements of target applications such as drug toxicity studies. [...] Read more.
Modular microfluidics offer the opportunity to combine the precise fluid control, rapid sample processing, low sample and reagent volumes, and relatively lower cost of conventional microfluidics with the flexible reconfigurability needed to accommodate the requirements of target applications such as drug toxicity studies. However, combining the capabilities of fully adaptable modular microelectromechanical systems (MEMS) assembly with the simplicity of conventional microfluidic fabrication remains a challenge. A hybrid polydimethylsiloxane (PDMS)-molding/photolithographic process is demonstrated to rapidly fabricate LEGO®-like modular blocks. The blocks are created with different sizes that interlock via tongue-and-groove joints in the plane and stack via interference fits out of the plane. These miniature strong but reversible connections have a measured resistance to in-plane and out-of-plane forces of up to >6000× and >1000× the weight of the block itself, respectively. The LEGO®-like interference fits enable O-ring-free microfluidic connections that withstand internal fluid pressures of >120 kPa. A single layer of blocks is assembled into LEGO®-like cell culture plates, where the in vitro biocompatibility and drug toxicity to lung epithelial adenocarcinoma cells and hepatocellular carcinoma cells cultured in the modular microwells are measured. A double-layer block structure is then assembled so that a microchannel formed at the interface between layers connects two microwells. Breast tumor cells and hepatocytes cultured in the coupled wells demonstrate interwell migration as well as the simultaneous effects of a single drug on the two cell types. Full article
(This article belongs to the Special Issue Microengineering Techniques for Disease Modeling and Drug Discovery)
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13 pages, 2879 KiB  
Article
Engineering a Bi-Conical Microchip as Vascular Stenosis Model
by Yan Li, Jianchun Wang, Wei Wan, Chengmin Chen, Xueying Wang, Pei Zhao, Yanjin Hou, Hanmei Tian, Jianmei Wang, Krishnaswamy Nandakumar and Liqiu Wang
Micromachines 2019, 10(11), 790; https://doi.org/10.3390/mi10110790 - 18 Nov 2019
Viewed by 3100
Abstract
Vascular stenosis is always associated with hemodynamic changes, especially shear stress alterations. Herein, bi-conical shaped microvessels were developed through flexibly and precisely controlled templated methods for hydrogel blood-vessel-like microchip. The blood-vessel-like microvessels demonstrated tunable dimensions, perfusable ability, and good cytocompatibility. The microchips showed [...] Read more.
Vascular stenosis is always associated with hemodynamic changes, especially shear stress alterations. Herein, bi-conical shaped microvessels were developed through flexibly and precisely controlled templated methods for hydrogel blood-vessel-like microchip. The blood-vessel-like microvessels demonstrated tunable dimensions, perfusable ability, and good cytocompatibility. The microchips showed blood-vessel-like lumens through fine embeddedness of human umbilical vein endothelial cells (HUVECs) on the interior surface of hydrogel microchannels, which closely reproduced the morphology and functions of human blood vessels. In the gradual narrowing region of bi-conical shape, fluid flow generated wall shear stress, which caused cell morphology variations. Wall shear rates at the gradual narrowing region were simulated by FLUENT software. The results showed that our microchannels qualified for performance as a vascular stenosis-like model in evaluating blood hydrodynamics. In general, our blood-vessel-on-a-chip could offer potential applications in the prevention, diagnosis, and therapy of arterial thrombosis. Full article
(This article belongs to the Special Issue Microengineering Techniques for Disease Modeling and Drug Discovery)
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Review

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18 pages, 2845 KiB  
Review
3D Printing Breast Tissue Models: A Review of Past Work and Directions for Future Work
by Chantell Cleversey, Meghan Robinson and Stephanie M. Willerth
Micromachines 2019, 10(8), 501; https://doi.org/10.3390/mi10080501 - 27 Jul 2019
Cited by 23 | Viewed by 7856
Abstract
Breast cancer often results in the removal of the breast, creating a need for replacement tissue. Tissue engineering offers the promise of generating such replacements by combining cells with biomaterial scaffolds and serves as an attractive potential alternative to current surgical repair methods. [...] Read more.
Breast cancer often results in the removal of the breast, creating a need for replacement tissue. Tissue engineering offers the promise of generating such replacements by combining cells with biomaterial scaffolds and serves as an attractive potential alternative to current surgical repair methods. Such engineered tissues can also serve as important tools for drug screening and provide in vitro models for analysis. 3D bioprinting serves as an exciting technology with significant implications and applications in the field of tissue engineering. Here we review the work that has been undertaken in hopes of generating the recognized in-demand replacement breast tissue using different types of bioprinting. We then offer suggestions for future work needed to advance this field for both in vitro and in vivo applications. Full article
(This article belongs to the Special Issue Microengineering Techniques for Disease Modeling and Drug Discovery)
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19 pages, 16483 KiB  
Review
Coupling Microfluidic Platforms, Microfabrication, and Tissue Engineered Scaffolds to Investigate Tumor Cells Mechanobiology
by Martial Millet, Raoua Ben Messaoud, Carole Luthold and Francois Bordeleau
Micromachines 2019, 10(6), 418; https://doi.org/10.3390/mi10060418 - 22 Jun 2019
Cited by 12 | Viewed by 5691
Abstract
The tumor microenvironment (TME) is composed of dynamic and complex networks composed of matrix substrates, extracellular matrix (ECM), non-malignant cells, and tumor cells. The TME is in constant evolution during the disease progression, most notably through gradual stiffening of the stroma. Within the [...] Read more.
The tumor microenvironment (TME) is composed of dynamic and complex networks composed of matrix substrates, extracellular matrix (ECM), non-malignant cells, and tumor cells. The TME is in constant evolution during the disease progression, most notably through gradual stiffening of the stroma. Within the tumor, increased ECM stiffness drives tumor growth and metastatic events. However, classic in vitro strategies to study the TME in cancer lack the complexity to fully replicate the TME. The quest to understand how the mechanical, geometrical, and biochemical environment of cells impacts their behavior and fate has been a major force driving the recent development of new technologies in cell biology research. Despite rapid advances in this field, many challenges remain in order to bridge the gap between the classical culture dish and the biological reality of actual tissue. Microfabrication coupled with microfluidic approaches aim to engineer the actual complexity of the TME. Moreover, TME bioengineering allows artificial modulations with single or multiple cues to study different phenomena occurring in vivo. Some innovative cutting-edge tools and new microfluidic approaches could have an important impact on the fields of biology and medicine by bringing deeper understanding of the TME, cell behavior, and drug effects. Full article
(This article belongs to the Special Issue Microengineering Techniques for Disease Modeling and Drug Discovery)
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