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Micromachines
Special Issues
3D In Vitro Tissue and Organ Models
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3D In Vitro Tissue and Organ Models

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

Deadline for manuscript submissions: closed (31 October 2021) | Viewed by 29344

Special Issue Editors

Dr. Nur Mustafaoglu

E-Mail Website
Guest Editor
Faculty of Engineering and Natural Sciences, Sabanci University, 34956 Istanbul, Turkey
Interests: organ-on-a-chip; blood-brain barrier; tissue engineering; mechanobiology; biosensing; disease detection; drug delivery; nanotherapeutics; nanobiotechnology
Prof. Vasif Hasirci

E-Mail Website
Guest Editor
Medical Engineering, Acibadem Mehmet Ali Aydinlar University, Istanbul 34752, Turkey
Interests: biomaterials; tissue engineering; 3D printing; additive manufacturing; nano-micropatterned surfaces; tissue-material interactions; drug delivery; hydrogels; tissue models
Dr. Ken Takahashi

E-Mail Website
Guest Editor
Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata Cho, Kita-Ward, Okayama 700-8558, Japan
Interests: cardiovascular regenerative medicine; ischemia-reperfusion injury; space medicine/biology
Special Issues, Collections and Topics in MDPI journals
Dr. Menekse Ermis

E-Mail Website
Guest Editor
Center of Excellence in Biomaterials and Tissue Engineering (BIOMATEN), Middle East Technical University, 06800 Ankara, Turkey
Interests: biomaterials; cancer; microfluidics; 3D printing; soft tissues; cell-material interactions

Special Issue Information

Dear Colleagues,

We use animal models to test medications to improve human health (in vivo or preclinical applications), though animal organisms are not identical to human ones, whose responses can only be evaluated in clinical testing. Studies in academia and the pharmaceutical industry have consistently shown that preclinical animal models for drug research have failed. In fact, the failure rates of animal experiments are as high as 90%, as a result of both ineffectiveness and safety issues when testing the drugs in human clinical trials. Recapitulating physiologically significant human organ and tissue functions in vitro, therefore, becomes crucial for the development of new therapeutics and life-saving innovations. In vitro organ models can be used as substitutes for human organ transplants (ex vivo applications) and as alternatives to animal models for toxicology testing. Worldwide, the scientific community is focusing on advancing new technologies for tissue engineering, cell biology, 3D printing, and microfluidics to overcome the problems associated with existing in vitro models. Undeniably, creative design concepts and the inclusion of the developmental and cellular biology of the target tissues or organs are moving us closer to this ultimate goal. In addition, developments in material science for the manufacture of scaffolds or microfluidic systems using specific techniques are contributing significantly to the reconstitution of cellular microenvironments for whole organs or functional human tissue units. Many in vitro human models, however, require further improvement, refinement, and/or validation to be considered as functional substitutes of tissues for drug testing that will replace preclinical animal studies or of organs for transplantation.

This Special Issue welcomes your submission of research manuscripts and review articles that are related to advancements in the fields of tissue engineering, cell biology, material sciences and nanoscience and address the current challenges in the development of in vitro human tissue and organ models.

Dr. Nur Mustafaoglu
Prof. Vasif Hasirci
Dr. Ken Takahashi
Dr. Menekse Ermis
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

  • Tissue Engineering
  • Tissue Models
  • Organ Models
  • In vitro Models
  • Microphysiological Systems
  • Organ Chips (organ on a chip)
  • Microfluidics
  • Organoids
  • Spheroids
  • Stem Cell Technologies
  • Primary Cells
  • Transwell Models
  • Whole Organ Scaffolds
  • 3D Tissue/Organ Printing
  • Decellularization
  • Recellularization

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Published Papers (5 papers)

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Research

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20 pages, 2604 KiB  
Article
A Cell Culture Chip with Transparent, Micropillar-Decorated Bottom for Live Cell Imaging and Screening of Breast Cancer Cells
by Menekse Ermis, Ezgi Antmen, Ozgur Kuren, Utkan Demirci and Vasif Hasirci
Micromachines 2022, 13(1), 93; https://doi.org/10.3390/mi13010093 - 7 Jan 2022
Cited by 3 | Viewed by 3337
Abstract
In the recent years, microfabrication technologies have been widely used in cell biology, tissue engineering, and regenerative medicine studies. Today, the implementation of microfabricated devices in cancer research is frequent and advantageous because it enables the study of cancer cells in controlled microenvironments [...] Read more.
In the recent years, microfabrication technologies have been widely used in cell biology, tissue engineering, and regenerative medicine studies. Today, the implementation of microfabricated devices in cancer research is frequent and advantageous because it enables the study of cancer cells in controlled microenvironments provided by the microchips. Breast cancer is one of the most common cancers in women, and the way breast cancer cells interact with their physical microenvironment is still under investigation. In this study, we developed a transparent cell culture chip (Ch-Pattern) with a micropillar-decorated bottom that makes live imaging and monitoring of the metabolic, proliferative, apoptotic, and morphological behavior of breast cancer cells possible. The reason for the use of micropatterned surfaces is because cancer cells deform and lose their shape and acto-myosin integrity on micropatterned substrates, and this allows the quantification of the changes in morphology and through that identification of the cancerous cells. In the last decade, cancer cells were studied on micropatterned substrates of varying sizes and with a variety of biomaterials. These studies were conducted using conventional cell culture plates carrying patterned films. In the present study, cell culture protocols were conducted in the clear-bottom micropatterned chip. This approach adds significantly to the current knowledge and applications by enabling low-volume and high-throughput processing of the cell behavior, especially the cell–micropattern interactions. In this study, two different breast cancer cell lines, MDA-MB-231 and MCF-7, were used. MDA-MB-231 cells are invasive and metastatic, while MCF-7 cells are not metastatic. The nuclei of these two cell types deformed to distinctly different levels on the micropatterns, had different metabolic and proliferation rates, and their cell cycles were affected. The Ch-Pattern chips developed in this study proved to have significant advantages when used in the biological analysis of live cells and highly beneficial in the study of screening breast cancer cell–substrate interactions in vitro. Full article
(This article belongs to the Special Issue 3D In Vitro Tissue and Organ Models)
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16 pages, 3860 KiB  
Article
A Personalized Glomerulus Chip Engineered from Stem Cell-Derived Epithelium and Vascular Endothelium
by Yasmin Roye, Rohan Bhattacharya, Xingrui Mou, Yuhao Zhou, Morgan A. Burt and Samira Musah
Micromachines 2021, 12(8), 967; https://doi.org/10.3390/mi12080967 - 16 Aug 2021
Cited by 37 | Viewed by 6590
Abstract
Progress in understanding kidney disease mechanisms and the development of targeted therapeutics have been limited by the lack of functional in vitro models that can closely recapitulate human physiological responses. Organ Chip (or organ-on-a-chip) microfluidic devices provide unique opportunities to overcome some of [...] Read more.
Progress in understanding kidney disease mechanisms and the development of targeted therapeutics have been limited by the lack of functional in vitro models that can closely recapitulate human physiological responses. Organ Chip (or organ-on-a-chip) microfluidic devices provide unique opportunities to overcome some of these challenges given their ability to model the structure and function of tissues and organs in vitro. Previously established organ chip models typically consist of heterogenous cell populations sourced from multiple donors, limiting their applications in patient-specific disease modeling and personalized medicine. In this study, we engineered a personalized glomerulus chip system reconstituted from human induced pluripotent stem (iPS) cell-derived vascular endothelial cells (ECs) and podocytes from a single patient. Our stem cell-derived kidney glomerulus chip successfully mimics the structure and some essential functions of the glomerular filtration barrier. We further modeled glomerular injury in our tissue chips by administering a clinically relevant dose of the chemotherapy drug Adriamycin. The drug disrupts the structural integrity of the endothelium and the podocyte tissue layers, leading to significant albuminuria as observed in patients with glomerulopathies. We anticipate that the personalized glomerulus chip model established in this report could help advance future studies of kidney disease mechanisms and the discovery of personalized therapies. Given the remarkable ability of human iPS cells to differentiate into almost any cell type, this work also provides a blueprint for the establishment of more personalized organ chip and ‘body-on-a-chip’ models in the future. Full article
(This article belongs to the Special Issue 3D In Vitro Tissue and Organ Models)
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20 pages, 3508 KiB  
Article
Fabrication of Stromal Cell-Derived Factor-1 Contained in Gelatin/Hyaluronate Copolymer Mixed with Hydroxyapatite for Use in Traumatic Bone Defects
by Yun-Liang Chang, Chia-Ying Hsieh, Chao-Yuan Yeh, Chih-Hao Chang and Feng-Huei Lin
Micromachines 2021, 12(7), 822; https://doi.org/10.3390/mi12070822 - 14 Jul 2021
Cited by 2 | Viewed by 2335
Abstract
Bone defects of orthopedic trauma remain a challenge in clinical practice. Regarding bone void fillers, besides the well-known osteoconductivity of most bone substitutes, osteoinductivity has also been gaining attention in recent years. It is known that stromal cell-derived factor-1 (SDF-1) can recruit mesenchymal [...] Read more.
Bone defects of orthopedic trauma remain a challenge in clinical practice. Regarding bone void fillers, besides the well-known osteoconductivity of most bone substitutes, osteoinductivity has also been gaining attention in recent years. It is known that stromal cell-derived factor-1 (SDF-1) can recruit mesenchymal stem cells (MSCs) in certain circumstances, which may also play an important role in bone regeneration. In this study, we fabricated a gelatin/hyaluronate (Gel/HA) copolymer mixed with hydroxyapatite (HAP) and SDF-1 to try and enhance bone regeneration in a bone defect model. After material characterization, these Gel/HA–HAP and Gel/HA–HAP–SDF-1 composites were tested for their biocompatibility and ability to recruit MSCs in vitro. A femoral condyle bone defect model of rats was used for in vivo studies. For the assessment of bone healing, micro-CT analysis, second harmonic generation (SHG) imaging, and histology studies were performed. As a result, the Gel/HA–HAP composites showed no systemic toxicity to rats. Gel/HA–HAP composite groups both showed better bone generation compared with the control group in an animal study, and the composite with the SDF-1 group even showed a trend of faster bone growth compared with the composite without SDF-1 group. In conclusion, in the management of traumatic bone defects, Gel/HA–HAP–SDF-1 composites can be a feasible material for use as bone void fillers. Full article
(This article belongs to the Special Issue 3D In Vitro Tissue and Organ Models)
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Review

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23 pages, 976 KiB  
Review
Drug-Induced Nephrotoxicity Assessment in 3D Cellular Models
by Pengfei Yu, Zhongping Duan, Shuang Liu, Ivan Pachon, Jianxing Ma, George P. Hemstreet and Yuanyuan Zhang
Micromachines 2022, 13(1), 3; https://doi.org/10.3390/mi13010003 - 21 Dec 2021
Cited by 18 | Viewed by 5029
Abstract
The kidneys are often involved in adverse effects and toxicity caused by exposure to foreign compounds, chemicals, and drugs. Early predictions of these influences are essential to facilitate new, safe drugs to enter the market. However, in current drug treatments, drug-induced nephrotoxicity accounts [...] Read more.
The kidneys are often involved in adverse effects and toxicity caused by exposure to foreign compounds, chemicals, and drugs. Early predictions of these influences are essential to facilitate new, safe drugs to enter the market. However, in current drug treatments, drug-induced nephrotoxicity accounts for 1/4 of reported serious adverse reactions, and 1/3 of them are attributable to antibiotics. Drug-induced nephrotoxicity is driven by multiple mechanisms, including altered glomerular hemodynamics, renal tubular cytotoxicity, inflammation, crystal nephropathy, and thrombotic microangiopathy. Although the functional proteins expressed by renal tubules that mediate drug sensitivity are well known, current in vitro 2D cell models do not faithfully replicate the morphology and intact renal tubule function, and therefore, they do not replicate in vivo nephrotoxicity. The kidney is delicate and complex, consisting of a filter unit and a tubular part, which together contain more than 20 different cell types. The tubular epithelium is highly polarized, and maintaining cellular polarity is essential for the optimal function and response to environmental signals. Cell polarity depends on the communication between cells, including paracrine and autocrine signals, as well as biomechanical and chemotaxis processes. These processes affect kidney cell proliferation, migration, and differentiation. For drug disposal research, the microenvironment is essential for predicting toxic reactions. This article reviews the mechanism of drug-induced kidney injury, the types of nephrotoxicity models (in vivo and in vitro models), and the research progress related to drug-induced nephrotoxicity in three-dimensional (3D) cellular culture models. Full article
(This article belongs to the Special Issue 3D In Vitro Tissue and Organ Models)
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33 pages, 3328 KiB  
Review
Design and Fabrication of Organ-on-Chips: Promises and Challenges
by Alireza Tajeddin and Nur Mustafaoglu
Micromachines 2021, 12(12), 1443; https://doi.org/10.3390/mi12121443 - 25 Nov 2021
Cited by 44 | Viewed by 9870
Abstract
The advent of the miniaturization approach has influenced the research trends in almost all disciplines. Bioengineering is one of the fields benefiting from the new possibilities of microfabrication techniques, especially in cell and tissue culture, disease modeling, and drug discovery. The limitations of [...] Read more.
The advent of the miniaturization approach has influenced the research trends in almost all disciplines. Bioengineering is one of the fields benefiting from the new possibilities of microfabrication techniques, especially in cell and tissue culture, disease modeling, and drug discovery. The limitations of existing 2D cell culture techniques, the high time and cost requirements, and the considerable failure rates have led to the idea of 3D cell culture environments capable of providing physiologically relevant tissue functions in vitro. Organ-on-chips are microfluidic devices used in this context as a potential alternative to in vivo animal testing to reduce the cost and time required for drug evaluation. This emerging technology contributes significantly to the development of various research areas, including, but not limited to, tissue engineering and drug discovery. However, it also brings many challenges. Further development of the technology requires interdisciplinary studies as some problems are associated with the materials and their manufacturing techniques. Therefore, in this paper, organ-on-chip technologies are presented, focusing on the design and fabrication requirements. Then, state-of-the-art materials and microfabrication techniques are described in detail to show their advantages and also their limitations. A comparison and identification of gaps for current use and further studies are therefore the subject of the final discussion. Full article
(This article belongs to the Special Issue 3D In Vitro Tissue and Organ Models)
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