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Biomedicines
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Organoid, Organ-on-Chip and Advanced 2D/3D Models for Human Tissue Engineering...
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Organoid, Organ-on-Chip and Advanced 2D/3D Models for Human Tissue Engineering Applications

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Biomedical Engineering and Materials".

Deadline for manuscript submissions: 30 September 2025 | Viewed by 1532

Special Issue Editor

Dr. Ahmad Salti

E-Mail Website
Guest Editor
Center for Medical Research, University Clinic for Ophthalmology and Optometry, Johannes Kepler University Linz, 4020 Linz, Austria
Interests: induced pluripotent stem cells (iPSCs); retinal organoids; brain organoids; neurodegenerative diseases; retinitis pigmentosa; Parkinson’s disease; in vitro models; brain development
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Organoids, organs-on-chips, and advanced 2D/3D models are promising and emerging cutting-edge technologies in human tissue engineering.

Organoids are three dimensional miniaturized, simplified versions of organs grown in vitro and derived from pluripotent stem cells. They mimic the structure and function of real organs, making them valuable for studying development, disease, and drug responses. On the other hand, organs-on-chips are microfluidic devices that simulate the activities, mechanics, and physiological responses of entire organs and organ systems. These chips integrate living cells into a 3D matrix, allowing for precise control over the cellular microenvironment and enabling high-throughput testing. Microfluidic systems are based on incorporating micro-channels capable of transporting specific fluids into either organs or organoids to ensure their interaction with the surrounding environment. Moreover, advanced 2D/3D models including both traditional 2D cell cultures and more complex 3D cultures, such as assembloids, can better replicate the in vivo environment and are crucial for understanding cell behavior, tissue development, and disease mechanisms. Together, these technologies can complement existing animal models by offering powerful tools for biomedical research, and providing more accurate and human-relevant models for drug testing, disease modeling, and regenerative medicine.

This Special Issue, “Organoid, Organ-on-Chip and Advanced 2D/3D Models for Human Tissue Engineering Applications”, aims to provide the latest insights into these promising technologies and how these techniques can contribute in disease modelling, cell replacing therapies and drug screening.

Dr. Ahmad Salti
Guest Editor

Manuscript Submission Information

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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. Biomedicines 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

  • organoid
  • organ-on-chip
  • 2D/3D model
  • tissue engineering
  • induced pluripotent stem cells
  • in vitro model

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Published Papers (2 papers)

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Research

20 pages, 4985 KiB  
Article
Patient-Oriented In Vitro Studies in Duchenne Muscular Dystrophy: Validation of a 3D Skeletal Muscle Organoid Platform
by Raffaella Quarta, Enrica Cristiano, Mitchell K. L. Han, Brigida Boccanegra, Manuel Marinelli, Nikolas Gaio, Jessica Ohana, Vincent Mouly, Ornella Cappellari and Annamaria De Luca
Biomedicines 2025, 13(5), 1109; https://doi.org/10.3390/biomedicines13051109 - 3 May 2025
Viewed by 318
Abstract
Background: Three-dimensional skeletal muscle organoids (3D SkMO) are becoming of increasing interest for preclinical studies in Duchenne muscular dystrophy (DMD), provided that the used platform demonstrates the possibility to form functional and reproducible 3D SkMOs, to investigate on potential patient-related phenotypic differences. Methods [...] Read more.
Background: Three-dimensional skeletal muscle organoids (3D SkMO) are becoming of increasing interest for preclinical studies in Duchenne muscular dystrophy (DMD), provided that the used platform demonstrates the possibility to form functional and reproducible 3D SkMOs, to investigate on potential patient-related phenotypic differences. Methods: In this study, we employed fibrin-based 3D skeletal muscle organoids derived from immortalized myogenic precursors of DMD patients carrying either a stop codon mutation in exon 59 or a 48–50 deletion. We compared dystrophic lines with a healthy wild-type control (HWT) by assessing microtissue formation ability, contractile function at multiple timepoints along with intracellular calcium dynamics via calcium imaging, as well as expression of myogenic markers. Results: We found patient-specific structural and functional differences in the early stages of 3D SkMO development. Contractile force, measured as both single twitch and tetanic responses, was significantly lower in dystrophic 3D SkMOs compared to HWT, with the most pronounced differences observed at day 7 of differentiation. However, these disparities diminished over time under similar culturing conditions and in the absence of continuous nerve-like stimulation, suggesting that the primary deficit lies in delayed myogenic maturation, as also supported by gene expression analysis. Conclusions: Our results underline that, despite the initial maturation delay, DMD muscle precursors retain the capacity to form functional 3D SkMOs once this intrinsic lag is overcome. This suggests a critical role of dystrophin in early myogenic development, while contraction-induced stress and/or an inflammatory microenvironment are essential to fully recapitulate dystrophic phenotypes in 3D SkMOs. Full article
(This article belongs to the Special Issue Organoid, Organ-on-Chip and Advanced 2D/3D Models for Human Tissue Engineering Applications)
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24 pages, 3411 KiB  
Article
Comparative Analysis of Proximal Tubule Cell Sources for In Vitro Studies of Renal Proximal Tubule Toxicity
by Courtney Sakolish, Han-Hsuan D. Tsai, Hsing-Chieh Lin, Piyush Bajaj, Remi Villenave, Stephen S. Ferguson, Jason P. Stanko, Richard A. Becker, Philip Hewitt, Weihsueh A. Chiu and Ivan Rusyn
Biomedicines 2025, 13(3), 563; https://doi.org/10.3390/biomedicines13030563 - 24 Feb 2025
Cited by 1 | Viewed by 753
Abstract
Background/Objectives: The kidneys are essential for eliminating drugs and chemicals from the human body and renal epithelial cells are particularly vulnerable to damage caused by xenobiotics and their metabolites. Drug-induced kidney toxicity is a major cause of drug attrition during preclinical and clinical [...] Read more.
Background/Objectives: The kidneys are essential for eliminating drugs and chemicals from the human body and renal epithelial cells are particularly vulnerable to damage caused by xenobiotics and their metabolites. Drug-induced kidney toxicity is a major cause of drug attrition during preclinical and clinical development and the ability to predict renal toxicity remains a pressing challenge, necessitating more predictive in vitro models. However, the abundance of commercially available renal proximal tubule epithelial cell (RPTEC) sources complicates the selection of the most predictive cell types. Methods: This study compared a wide range of RPTEC sources, including primary cells (Lonza) and various RPTEC lines from different vendors, such as ciPTECs (Cell4Pharma), TERT1/RPTECs (ATCC), and HEK293 (GenoMembrane), including OAT1-overexpressing variants. HepG2 cells were included for a comparison of organ specificity. The different cells were cultured in 96- or 384-well plates and exposed to 12 drugs for 72 h at a concentration yielding a response (0.3–300 µM) to evaluate their ability to predict clinical outcomes. The CellTiterGlo® assay was used to measure cell viability, and transcriptome data from unexposed cells was analyzed using the TempO-seq® S1500+ platform. Results: Gene expression data showed that the primary kidney cells most closely matched the transcriptome of the human kidney medulla, followed by the TERT1 and ciPTEC lines, with the HEK lines showing the lowest similarity. The RPTEC sources showed clustering by cell type, with OAT1 overexpression driving changes in metabolic, detoxification, and immune pathways, especially in TERT1 cells. Cell viability data were used to determine points of departure (PODs) which were compared to human serum Cmax values to assess safety margins. The TERT1 and ciPTEC RPTEC lines demonstrated the highest predictive performance for nephrotoxicity, with OAT1 overexpression significantly enhancing sensitivity, accuracy, and overall predictive power (MCC scores: 0.764 and 0.667, respectively). In contrast, HepG2 cells showed the lowest performance across all metrics, highlighting the critical role of cell type and transporter expression in nephrotoxicity prediction. Conclusions: This study highlights important differences among RPTEC sources and their utility in drug safety studies of the renal proximal tubule. We show that while improved cell options for renal proximal tubule are needed, OAT1-overexpressing RPTECs are a superior model to the background cell type. Full article
(This article belongs to the Special Issue Organoid, Organ-on-Chip and Advanced 2D/3D Models for Human Tissue Engineering Applications)
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