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Organoids and Advanced 3D Models in Biomedical Research

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A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Biological and Bio- Materials".

Deadline for manuscript submissions: closed (25 January 2024) | Viewed by 10800

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Special Issue Editor

Dr. Marta Alves da Silva

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Guest Editor

Laboratory Animal Science Group, i3S-Instituto de Investigação e Inovação em Saúde, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal
Interests: organoids; stem cells; advanced 3D models; microfluidics; disease modelling; regenerative medicine; tissue engineering
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We are pleased to invite you to submit your paper to our special issue on Organoids and Advanced 3D in vitro models.

Biomedical research faces a demanding need for the replacement of animal experiments by reliable, safe, and accurate in vitro models that fully recapitulate the structure and function of human tissues. Advances in stem cells bioengineering enabled adult stem cells (ASCs) and induced pluripotent stem cells (iPSCs) long-term culture in a 3D cellular structure named organoids. They recreate cellular architecture; are functionally similar to the tissue they are modeling and their use as models allow research without confusing influences from the local microenvironment.

This Special Issue aims to disseminate state-of-the-art science around organoid model systems, covering organoids models in 3D microenvironments, genetic engineering of organoids and microphysiologic systems, as well as methods for improving organoids culture and high throughput screening.

In this Special Issue, original research articles and reviews are welcome. Research areas may include (but not limited to) the following: disease modeling, personalized medicine, drug screening, tissue engineering, biomaterials, regenerative medicine and 3Rs.

I look forward to receiving your contributions.

You may choose our Joint Special Issue in Organoids.

Dr. Marta Alves da Silva
Guest Editor

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. Biomolecules 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

organoids
in vitro models
microenvironment
regenerative medicine
non-animal models
microfluidics

Published Papers (5 papers)

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Research

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16 pages, 9639 KiB

Open AccessArticle

Hyaluronic Acid Prevents Fusion of Brain Tumor-Derived Spheroids and Selectively Alters Their Gene Expression Profile

by Irina Arutyunyan, Anna Soboleva, Dorzhu Balchir, Enar Jumaniyazova, Vera Kudelkina, Andrey Elchaninov and Timur Fatkhudinov

Biomolecules 2024, 14(4), 466; https://doi.org/10.3390/biom14040466 - 10 Apr 2024

Viewed by 869

Abstract

Hyaluronic acid (HA), a major glycosaminoglycan of the brain extracellular matrix, modulates cell behaviors through binding its receptor, Cd44. In this study, we assessed the influence of HA on high-grade brain tumors in vitro. The model comprised cell cultures derived from six rodent carcinogen-induced brain tumors, forming 3D spheroids prone to spontaneous fusion. Supplementation of the standard culture medium with 0.25% HA significantly inhibited the fusion rates, preserving the shape and size uniformity of spheroids. The 3D cultures were assigned to two groups; a Cd44lo group had a tenfold decreased relative expression of Cd44 than another (Cd44hi) group. In addition, these two groups differed by expression levels of Sox2 transcription factor; the correlation analysis revealed a tight negative association for Cd44 and Sox2. Transcriptomic responses of spheroids to HA exposure also depended on Cd44 expression levels, from subtle in Cd44lo to more pronounced and specific in Cd44hi, involving cell cycle progression, PI3K/AKT/mTOR pathway activation, and multidrug resistance genes. The potential HA-induced increase in brain tumor 3D models’ resistance to anticancer drug therapy should be taken into account when designing preclinical studies using HA scaffold-based models. The property of HA to prevent the fusion of brain-derived spheroids can be employed in CNS regenerative medicine and experimental oncology to ensure the production of uniform, controllably fusing neurospheres when creating more accurate in vitro brain models. Full article

(This article belongs to the Special Issue Organoids and Advanced 3D Models in Biomedical Research)

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23 pages, 4663 KiB

Open AccessArticle

Considering the Value of 3D Cultures for Enhancing the Understanding of Adhesion, Proliferation, and Osteogenesis on Titanium Dental Implants

by Federico Ferro, Federico Azzolin, Renza Spelat, Lorenzo Bevilacqua and Michele Maglione

Biomolecules 2023, 13(7), 1048; https://doi.org/10.3390/biom13071048 - 28 Jun 2023

Cited by 1 | Viewed by 1094

Abstract

Background: Individuals with pathologic conditions and restorative deficiencies might benefit from a combinatorial approach encompassing stem cells and dental implants; however, due to the various surface textures and coatings, the influence of titanium dental implants on cells exhibits extensive, wide variations. Three-dimensional (3D) cultures of stem cells on whole dental implants are superior in testing implant properties and were used to examine their capabilities thoroughly. Materials and methods: The surface micro-topography of five titanium dental implants manufactured by sandblasting with titanium, aluminum, corundum, or laser sintered and laser machined was compared in this study. After characterization, including particle size distribution and roughness, the adhesion, proliferation, and viability of adipose-derived stem cells (ADSCs) cultured on the whole-body implants were tested at three time points (one to seven days). Finally, the capacity of the implant to induce ADSCs’ spontaneous osteoblastic differentiation was examined at the same time points, assessing the gene expression of collagen type 1 (coll-I), osteonectin (osn), alkaline phosphatase (alp), and osteocalcin (osc). Results: Laser-treated (Laser Mach and Laser Sint) implants exhibited the highest adhesion degree; however, limited proliferation was observed, except for Laser Sint implants, while viability differences were seen throughout the three time points, except for Ti Blast implants. Sandblasted surfaces (Al Blast, Cor Blast, and Ti Blast) outpaced the laser-treated ones, inducing higher amounts of coll-I, osn, and alp, but not osc. Among the sandblasted surfaces, Ti Blast showed moderate roughness and the highest superficial texture density, favoring the most significant spontaneous differentiation relative to all the other implant surfaces. Conclusions: The results indicate that 3D cultures of stem cells on whole-body titanium dental implants is a practical and physiologically appropriate way to test the biological characteristics of the implants, revealing peculiar differences in ADSCs’ adhesion, proliferation, and activity toward osteogenic commitment in the absence of specific osteoinductive cues. In addition, the 3D method would allow researchers to test various implant surfaces more thoroughly. Integrating with preconditioned stem cells would inspire a more substantial combinatorial approach to promote a quicker recovery for patients with restorative impairments. Full article

(This article belongs to the Special Issue Organoids and Advanced 3D Models in Biomedical Research)

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Review

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19 pages, 1504 KiB

Open AccessReview

Alveolar Organoids in Lung Disease Modeling

by Enkhee Purev, Karim Bahmed and Beata Kosmider

Biomolecules 2024, 14(1), 115; https://doi.org/10.3390/biom14010115 - 16 Jan 2024

Cited by 1 | Viewed by 2440

Abstract

Lung organoids display a tissue-specific functional phenomenon and mimic the features of the original organ. They can reflect the properties of the cells, such as morphology, polarity, proliferation rate, gene expression, and genomic profile. Alveolar type 2 (AT2) cells have a stem cell potential in the adult lung. They produce and secrete pulmonary surfactant and proliferate to restore the epithelium after damage. Therefore, AT2 cells are used to generate alveolar organoids and can recapitulate distal lung structures. Also, AT2 cells in human-induced pluripotent stem cell (iPSC)-derived alveolospheres express surfactant proteins and other factors, indicating their application as suitable models for studying cell–cell interactions. Recently, they have been utilized to define mechanisms of disease development, such as COVID-19, lung cancer, idiopathic pulmonary fibrosis, and chronic obstructive pulmonary disease. In this review, we show lung organoid applications in various pulmonary diseases, drug screening, and personalized medicine. In addition, stem cell-based therapeutics and approaches relevant to lung repair were highlighted. We also described the signaling pathways and epigenetic regulation of lung regeneration. It is critical to identify novel regulators of alveolar organoid generations to promote lung repair in pulmonary diseases. Full article

(This article belongs to the Special Issue Organoids and Advanced 3D Models in Biomedical Research)

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23 pages, 8291 KiB

Open AccessReview

3D Organoids for Regenerative Endodontics

by Fang-Chi Li and Anil Kishen

Biomolecules 2023, 13(6), 900; https://doi.org/10.3390/biom13060900 - 28 May 2023

Cited by 3 | Viewed by 2845

Abstract

Apical periodontitis is the inflammation and destruction of periradicular tissues, mediated by microbial factors originating from the infected pulp space. This bacteria-mediated inflammatory disease is known to interfere with root development in immature permanent teeth. Current research on interventions in immature teeth has been dedicated to facilitating the continuation of root development as well as regenerating the dentin–pulp complex, but the fundamental knowledge on the cellular interactions and the role of periapical mediators in apical periodontitis in immature roots that govern the disease process and post-treatment healing is limited. The limitations in 2D monolayer cell culture have a substantial role in the existing limitations of understanding cell-to-cell interactions in the pulpal and periapical tissues. Three-dimensional (3D) tissue constructs with two or more different cell populations are a better physiological representation of in vivo environment. These systems allow the high-throughput testing of multi-cell interactions and can be applied to study the interactions between stem cells and immune cells, including the role of mediators/cytokines in simulated environments. Well-designed 3D models are critical for understanding cellular functions and interactions in disease and healing processes for future therapeutic optimization in regenerative endodontics. This narrative review covers the fundamentals of (1) the disease process of apical periodontitis; (2) the influence and challenges of regeneration in immature roots; (3) the introduction of and crosstalk between mesenchymal stem cells and macrophages; (4) 3D cell culture techniques and their applications for studying cellular interactions in the pulpal and periapical tissues; (5) current investigations on cellular interactions in regenerative endodontics; and, lastly, (6) the dental–pulp organoid developed for regenerative endodontics. Full article

(This article belongs to the Special Issue Organoids and Advanced 3D Models in Biomedical Research)

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16 pages, 7222 KiB

Open AccessReview

Modeling Autism Spectrum Disorders with Induced Pluripotent Stem Cell-Derived Brain Organoids

by John Lenon de Souza Santos, Cecília de Almeida Araújo, Clarissa Araújo Gurgel Rocha, Zaquer Suzana Munhoz Costa-Ferro and Bruno Solano de Freitas Souza

Biomolecules 2023, 13(2), 260; https://doi.org/10.3390/biom13020260 - 30 Jan 2023

Cited by 5 | Viewed by 2884

Abstract

Autism spectrum disorders (ASD) are a group of complex neurodevelopmental disorders that affect communication and social interactions and present with restricted interests and repetitive behavior patterns. The susceptibility to ASD is strongly influenced by genetic/heritable factors; however, there is still a large gap in understanding the cellular and molecular mechanisms underlying the neurobiology of ASD. Significant progress has been made in identifying ASD risk genes and the possible convergent pathways regulated by these gene networks during development. The breakthrough of cellular reprogramming technology has allowed the generation of induced pluripotent stem cells (iPSCs) from individuals with syndromic and idiopathic ASD, providing patient-specific cell models for mechanistic studies. In the past decade, protocols for developing brain organoids from these cells have been established, leading to significant advances in the in vitro reproducibility of the early steps of human brain development. Here, we reviewed the most relevant literature regarding the application of brain organoids to the study of ASD, providing the current state of the art, and discussing the impact of such models on the field, limitations, and opportunities for future development. Full article

(This article belongs to the Special Issue Organoids and Advanced 3D Models in Biomedical Research)

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