3D Cultures and Organ-on-a-Chip in Cell and Tissue Cultures

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Methods".

Deadline for manuscript submissions: 25 October 2025 | Viewed by 518

Special Issue Editors


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Guest Editor
Department of Bioscience and Agro-Food and Environmental Technology, University of Teramo, via Renato Balzarini 1, 64100 Teramo, Italy
Interests: cell biology; biology of stem cells; biology of reproduction; ovarian angiogenesis; signal transduction; molecular biology; tissue regeneration; regenerative medicine; cancer; histology
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
Department of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, via Renato Balzarini 1, 64100 Teramo, Italy
Interests: cell biology; biology of amniotic derived stem cells; tissue regeneration; regenerative medicine; biology of reproduction; ovarian angiogenesis; signal transduction; molecular biology; advanced reproductive biotechnology techniques
Special Issues, Collections and Topics in MDPI journals

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Guest Editor

Special Issue Information

Dear Colleagues,

Our Special Issue “3D Cultures and Organ-on-a-Chip in Cell and Tissue Cultures” will highlight the transformative shift in tissue engineering and regenerative medicine. This evolution addresses the limitations of traditional two-dimensional (2D) cell culture models, which often fail to replicate the complex physiological environments of living organisms. In contrast, three-dimensional (3D) cell culture methods and organ-on-a-chip technologies provide advanced platforms that closely mimic in vivo conditions, enhancing cellular behavior, differentiation, and interaction.

Furthermore, organ-on-a-chip platforms combine microfluidic technology and living cells to replicate organ-specific microenvironments, allowing for more accurate research on toxicity, physiology, and pharmacological reactions. Drug discovery and illness research are accelerated through the combination of 3D cultures and organ-on-a-chip technologies, which opens up new possibilities for customized treatment. In this context, in recent decades, several models using different organs (lungs on a chip, liver on a chip, kidney on a chip, heart on a chip, intestine on a chip, and skin on a chip) have been successfully developed. However, relatively little research has been carried out on a number of other organs (such as the retina, placenta, and ovaries).

These new techniques have seen increasing implications in virtually all fields in biotechnology, in particular, regenerative medicine, providing a wealth of opportunities, including drug toxicity and efficacy studies, in vitro analyses of biochemicals, and pathogenesis studies on diseases and metabolic activities in cells, in human and veterinary medicine, contributing to the investigation of both basic and application issues.

Thus, for this Special Issue, we welcome the submission of original articles, reviews and mini-reviews, method papers, brief research reports, and perspectives that illustrate and simulate the growing efforts to achieve the convergence of 3D cultures and organ-on-a-chip technologies for new opportunities for regenerative medicine, tissue engineering, and personalized medicine. These technologies could accelerate drug development and disease research while reducing our reliance on animal models, providing new insights and future trends in these rapidly evolving fields.

Prof. Dr. Annunziata Mauro
Prof. Dr. Barbara Barboni
Dr. Giovanna Della Porta
Guest Editors

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Keywords

  • three-dimensional cell culture
  • organ-on-a-chip
  • tissue engineering
  • regenerative medicine
  • drug testing
  • microfluidics
  • in vitro models
  • personalized medicine
  • cellular interaction
  • disease modeling

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Published Papers (1 paper)

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Review

35 pages, 2316 KiB  
Review
Modeling Tumor Microenvironment Complexity In Vitro: Spheroids as Physiologically Relevant Tumor Models and Strategies for Their Analysis
by Shrey Shah and Gerard G. M. D’Souza
Cells 2025, 14(10), 732; https://doi.org/10.3390/cells14100732 - 17 May 2025
Viewed by 234
Abstract
Drug delivery to solid tumors is challenged by multiple physiological barriers arising from the tumor microenvironment, including dense extracellular matrix, cellular heterogeneity, hypoxic gradients, and elevated interstitial fluid pressure. These features hinder the uniform distribution and accumulation of therapeutics, reducing treatment efficacy. Despite [...] Read more.
Drug delivery to solid tumors is challenged by multiple physiological barriers arising from the tumor microenvironment, including dense extracellular matrix, cellular heterogeneity, hypoxic gradients, and elevated interstitial fluid pressure. These features hinder the uniform distribution and accumulation of therapeutics, reducing treatment efficacy. Despite their widespread use, conventional two-dimensional monolayer cultures fail to reproduce these complexities, contributing to the poor translational predictability of many preclinical candidates. Three-dimensional multicellular tumor spheroids have emerged as more representative in vitro models that capture essential features of tumor architecture, stromal interactions, and microenvironmental resistance mechanisms. Spheroids exhibit spatially organized regions of proliferation, quiescence, and hypoxia, and can incorporate non-tumor cells to mimic tumor–stroma crosstalk. Advances in spheroid analysis now enable detailed evaluation of drug penetration, cellular migration, cytotoxic response, and molecular gradients using techniques such as optical and confocal imaging, large-particle flow cytometry, biochemical viability assays, and microfluidic integration. By combining physiological relevance with analytical accessibility, spheroid models support mechanistic studies of drug transport and efficacy under tumor-like conditions. Their adoption into routine preclinical workflows has the potential to improve translational accuracy while reducing reliance on animal models. Full article
(This article belongs to the Special Issue 3D Cultures and Organ-on-a-Chip in Cell and Tissue Cultures)
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