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Application of Bioengineered Models in Disease Modeling and Organ Regeneration

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A special issue of Bioengineering (ISSN 2306-5354). This special issue belongs to the section "Regenerative Engineering".

Deadline for manuscript submissions: 20 September 2024 | Viewed by 5722

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Special Issue Editors

Dr. Chandani Sen

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Guest Editor

Pediatrics Department, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
Interests: 3D models; organoids; organ-on-a-chip; biomechanics; biomaterials; disease modeling; drug screening

Dr. Kalpana Mandal

E-Mail Website
Guest Editor

Terasaki Institute for Biomedical Innovation, University of Pennsylvania, Philadelphia, PA, USA
Interests: organ-on-a-chip; cancer immunotherapy; microfluidics; 3D model system for drug delivery; cell mechanics; traction force; optical tweezers

Prof. Dr. Amol V. Janorkar

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Guest Editor

Biomedical Materials Science, School of Dentistry, University of Mississippi Medical Center, Jackson, MS 39216, USA
Interests: synthesis and modification of polymeric biomaterials; tissue engineering; multi-component drug delivery systems; in vitro tissue and disease models
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

To overcome the limitations of the traditional monolayer-culture-in-a-dish, there has been a renewed effort to develop improved bioengineered model systems (organoids/organ-chips) that better recapitulate the structure and biology of native human organ and, by extension, their development and diseases. Successful generation of these models requires the convergence of biology and engineering expertise to recreate the microstructural, histological, and functional properties of the native organ. Bioengineered models are needed for improving the in vitro preclinical disease models for drug testing, as well as allowing a deeper understanding of different developmental stages at the molecular and cellular level that can lead to organ regeneration.

In this Special Issue, we invite original research work, as well as reviews on development and application of novel bioengineered microphysiological model systems. Topics of interest include, but are not limited to:

Advanced experimental methods for developing bioengineered models, such as organoid, organ-chip, synergistic system (organoid+ organ-chip), etc.;
Advancements in related technologies such as biomaterials, scaffold engineering, microfluidics, 3D printing, microfabrication, 3D imaging, quantification, etc.;
Application of bioengineered models for disease modeling and drug screening;
Application of bioengineered models to study organ development and regeneration.

Dr. Chandani Sen
Dr. Kalpana Mandal
Prof. Dr. Amol V. Janorkar
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. Bioengineering 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 2700 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

organoid
organ-chip
biomaterials
microphysiological systems
3D printing
disease modeling
organ regeneration

Published Papers (4 papers)

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Research

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10 pages, 2203 KiB

Open AccessCommunication

Application of Adipose Stem Cells in 3D Nerve Guidance Conduit Prevents Muscle Atrophy and Improves Distal Muscle Compliance in a Peripheral Nerve Regeneration Model

by Cristian Trâmbițaș, Bogdan Andrei Cordoș, Dorin Constantin Dorobanțu, Cristian Vintilă, Alexandru Petru Ion, Timea Pap, David Camelia, Claudiu Puiac, Emil Marian Arbănași, Claudiu Constantin Ciucanu, Adrian Vasile Mureșan, Eliza Mihaela Arbănași and Eliza Russu

Bioengineering 2024, 11(2), 184; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering11020184 - 15 Feb 2024

Viewed by 827

Abstract

Background: Peripheral nerve injuries (PNIs) represent a significant clinical problem, and standard approaches to nerve repair have limitations. Recent breakthroughs in 3D printing and stem cell technologies offer a promising solution for nerve regeneration. The main purpose of this study was to examine the biomechanical characteristics in muscle tissue distal to a nerve defect in a murine model of peripheral nerve regeneration from physiological stress to failure. Methods: In this experimental study, we enrolled 18 Wistar rats in which we created a 10 mm sciatic nerve defect. Furthermore, we divided them into three groups as follows: in Group 1, we used 3D nerve guidance conduits (NGCs) and adipose stem cells (ASCs) in seven rats; in Group 2, we used only 3D NGCs for seven rats; and in Group 3, we created only the defect in four rats. We monitored the degree of atrophy at 4, 8, and 12 weeks by measuring the diameter of the tibialis anterior (TA) muscle. At the end of 12 weeks, we took the TA muscle and analyzed it uniaxially at 10% stretch until failure. Results: In the group of animals with 3D NGCs and ASCs, we recorded the lowest degree of atrophy at 4 weeks, 8 weeks, and 12 weeks after nerve reconstruction. At 10% stretch, the control group had the highest Cauchy stress values compared to the 3D NGC group (0.164 MPa vs. 0.141 MPa, p = 0.007) and the 3D NGC + ASC group (0.164 MPa vs. 0.123 MPa, p = 0.007). In addition, we found that the control group (1.763 MPa) had the highest TA muscle stiffness, followed by the 3D NGC group (1.412 MPa), with the best muscle elasticity showing in the group in which we used 3D NGC + ASC (1.147 MPa). At failure, TA muscle samples from the 3D NGC + ASC group demonstrated better compliance and a higher degree of elasticity compared to the other two groups (p = 0.002 and p = 0.008). Conclusions: Our study demonstrates that the combination of 3D NGC and ASC increases the process of nerve regeneration and significantly improves the compliance and mechanical characteristics of muscle tissue distal to the injury site in a PNI murine model. Full article

(This article belongs to the Special Issue Application of Bioengineered Models in Disease Modeling and Organ Regeneration)

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17 pages, 4872 KiB

Open AccessArticle

Organotypic 3D Co-Culture of Human Pleura as a Novel In Vitro Model of Staphylococcus aureus Infection and Biofilm Development

by Olga Kurow, Rima Nuwayhid, Peggy Stock, Matthias Steinert, Stefan Langer, Sebastian Krämer and Isabella B. Metelmann

Bioengineering 2023, 10(5), 537; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering10050537 - 27 Apr 2023

Cited by 2 | Viewed by 1251

Abstract

Bacterial pleural infections are associated with high mortality. Treatment is complicated due to biofilm formation. A common causative pathogen is Staphylococcus aureus (S. aureus). Since it is distinctly human-specific, rodent models do not provide adequate conditions for research. The purpose of this study was to examine the effects of S. aureus infection on human pleural mesothelial cells using a recently established 3D organotypic co-culture model of pleura derived from human specimens. After infection of our model with S. aureus, samples were harvested at defined time points. Histological analysis and immunostaining for tight junction proteins (c-Jun, VE-cadherin, and ZO-1) were performed, demonstrating changes comparable to in vivo empyema. The measurement of secreted cytokine levels (TNF-α, MCP-1, and IL-1β) proved host–pathogen interactions in our model. Similarly, mesothelial cells produced VEGF on in vivo levels. These findings were contrasted by vital, unimpaired cells in a sterile control model. We were able to establish a 3D organotypic in vitro co-culture model of human pleura infected with S. aureus resulting in the formation of biofilm, including host–pathogen interactions. This novel model could be a useful microenvironment tool for in vitro studies on biofilm in pleural empyema. Full article

(This article belongs to the Special Issue Application of Bioengineered Models in Disease Modeling and Organ Regeneration)

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12 pages, 2419 KiB

Open AccessArticle

The Selective α1 Antagonist Tamsulosin Alters ECM Distributions and Cellular Metabolic Functions of ARPE 19 Cells in a Concentration-Dependent Manner

by Yosuke Ida, Tatsuya Sato, Megumi Watanabe, Araya Umetsu, Yuri Tsugeno, Masato Furuhashi, Fumihito Hikage and Hiroshi Ohguro

Bioengineering 2022, 9(10), 556; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering9100556 - 14 Oct 2022

Cited by 1 | Viewed by 1433

Abstract

The purpose of the present study was to examine the effect of the selective α1 antagonist tamsulosin (TAM) on human retinal pigment epithelium cells, ARPE 19. Two-dimension (2D) and three-dimension (3D) cultured ARPE 19 cells were used in the following characterizations: (1) ultrastructure by scanning electron microscopy (SEM) (2D); (2) barrier functions by transepithelial electrical resistance (TEER) measurements, and FITC-dextran permeability (2D); (3) real time cellular metabolisms by Seahorse Bioanalyzer (2D); (4) physical properties, size and stiffness measurements (3D); and (5) expression of extracellular matrix (ECM) proteins, including collagen1 (COL1), COL4, COL6 and fibronectin (FN) by qPCR and immunohistochemistry (2D and 3D). TAM induced significant effects including: (1) alteration of the localization of the ECM deposits; (2) increase and decrease of the TEER values and FITC-dextran permeability, respectively; (3) energy shift from glycolysis into mitochondrial oxidative phosphorylation (OXPHOS); (4) large and stiffened 3D spheroids; and (5) down-regulations of the mRNA expressions and immune labeling of most ECM proteins in a concentration-dependent manner. However, in some ECM proteins, COL1 and COL6, their immunolabeling intensities were increased at the lowest concentration (1 μM) of TAM. Such a discrepancy between the gene expressions and immunolabeling of ECM proteins may support alterations of ECM localizations as observed by SEM. The findings reported herein indicate that the selective α1 antagonist, TAM, significantly influenced ECM production and distribution as well as cellular metabolism levels in a concentration-dependent manner. Full article

(This article belongs to the Special Issue Application of Bioengineered Models in Disease Modeling and Organ Regeneration)

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Review

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16 pages, 881 KiB

Open AccessReview

Experimental Models for Rare Melanoma Research—The Niche That Needs to Be Addressed

by Ioana Ionita, Daniel Malita, Cristina Dehelean, Emilian Olteanu, Iasmina Marcovici, Andreea Geamantan, Sorin Chiriac, Andrea Roman and Daniela Radu

Bioengineering 2023, 10(6), 673; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering10060673 - 01 Jun 2023

Cited by 1 | Viewed by 1415

Abstract

Melanoma, the tumor arising from the malignant transformation of pigment-producing cells—the melanocytes—represents one of the most severe cancer types. Despite their rarity compared to cutaneous melanoma, the extracutaneous subtypes such as uveal melanoma (UM), acral lentiginous melanoma (ALM), and mucosal melanoma (MM) stand out due to their increased aggressiveness and mortality rate, demanding continuous research to elucidate their specific pathological features and develop efficient therapies. Driven by the emerging progresses made in the preclinical modeling of melanoma, the current paper covers the most relevant in vitro, in vivo, and in ovo systems, providing a deeper understanding of these rare melanoma subtypes. However, the preclinical models for UM, ALM, and MM that were developed so far remain scarce, and none of them is able to completely simulate the complexity that is characteristic to these melanomas; thus, a continuous expansion of the existing library of experimental models is pivotal for driving advancements in this research field. An overview of the applicability of precision medicine in the management of rare melanoma subtypes is also provided. Full article

(This article belongs to the Special Issue Application of Bioengineered Models in Disease Modeling and Organ Regeneration)

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