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Cells
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Recent Advances in Microfluidics and Organoids for Biomedical Applications
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Recent Advances in Microfluidics and Organoids for Biomedical Applications

A Special Issue of Cells (ISSN 2073-4409) belonging to the section "Tissues and Organs".

Deadline for manuscript submissions: closed (28 February 2026) | Viewed by 10505

Editor

Prof. Dr. Lionel Fernel Gamarra

E-Mail Website
Guest Editor
Einstein's Teaching and Research Institute, Hospital israleita Albert Einstien, São Paulo 05652-900, Brazil
Interests: nanomaterials; magnetic nanoparticles; nanomedicine; therapy; diagnosis; theranostic; cancer; neurodegenerative diseases; magnetic hyperthermia; lab-on-a-chip; molecular imaging; regenerative medicine
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Advances in microfluidics and organoids have revolutionized biomedicine by providing biomimetic models that overcome the limitations of traditional cell cultures and animal models. These technologies enable the precise control of microenvironments, cellular interactions, and dynamic physiological conditions, fostering breakthroughs in tissue engineering, pharmacology, toxicology, and regenerative medicine.

Microfluidics allows for controlled fluid dynamics, gradient formation, and real-time cellular monitoring, making it a key tool for studying biological barriers, drug delivery, and disease modeling. Meanwhile, organoids, derived from stem cells, offer 3D tissue architectures that better recapitulate developmental processes, disease progression, and therapeutic responses.

These platforms also play a crucial role in nanomedicine, supporting the development of nanoparticle-based therapies, biosensors, and advanced preclinical models.

This Special Issue welcomes original research, reviews, and perspectives on microfluidics and organoids, including the following:

  • Development of microfluidic devices for tissue modeling, drug screening, and physiological microenvironment simulation;
  • Innovations in organoid bioengineering, including enhanced tissue maturation, vascularization, and phenotypic stability;
  • Microfluidic platforms for toxicity testing and safety assessment of new compounds;
  • Advanced cell culture and differentiation strategies for creating more complex and functional organoids;
  • Integration of biosensors and live imaging techniques for real-time monitoring of organoids and microfluidic systems;
  • Computational modeling and artificial intelligence applied to the optimization of microfluidic and organoid systems;
  • Applications in nanomedicine, including nanoparticle-based therapies, nanobiosensor development, and toxicity testing in biomimetic platforms.

We invite contributions that explore how these technologies are shaping the future of biomedicine, the pharmaceutical industry, and translational research.

Dr. Lionel Fernel Gamarra
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 communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

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-anonymized peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly 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

  • microfluidics
  • organoids
  • biomimetic models
  • organ-on-a-chip
  • tissue engineering
  • pharmacology
  • biosensors
  • computational modeling
  • artificial intelligence
  • nanomedicine
  • personalized medicine
  • bioprinting
  • in silico
  • induced pluripotent stem cells (iPSCs)
  • mesenchymal and pluripotent stem cells

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Further information on MDPI's Special Issue policies can be found here.

Published Papers (6 papers)

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Research

Jump to: Review

15 pages, 4256 KB  
Article
Development of Supercooling Preservation Method for Adherently Cultured Endothelial Cells and Its Application to Microphysiological Systems
by Maaya Hikichi, Tsutomu Shimoda and Kiichi Sato
Cells 2026, 15(7), 619; https://doi.org/10.3390/cells15070619 - 30 Mar 2026
Viewed by 794
Abstract
Microphysiological systems (MPS) that recapitulate human organ functions have gained attention as alternatives to animal experiments in drug discovery, regenerative medicine, and toxicity assessments. However, preserving MPS with adherent cells remains a significant challenge. In this study, we developed a supercooling preservation method [...] Read more.
Microphysiological systems (MPS) that recapitulate human organ functions have gained attention as alternatives to animal experiments in drug discovery, regenerative medicine, and toxicity assessments. However, preserving MPS with adherent cells remains a significant challenge. In this study, we developed a supercooling preservation method that enables the low-temperature storage of human-derived adherent cells without freezing. Using human hepatic sinusoidal endothelial cells (TMNK-1), we optimized the preservation conditions by assessing the temperature, cooling and rewarming rates, and preservation solutions. Under optimized conditions (preservation at −4 °C, −0.028 °C/min cooling, and +1.0 °C/min rewarming), high cell viability and preserved morphology were maintained for up to 7 days. When these conditions were applied to both two- and three-dimensional MPS containing TMNK-1 or HepG2 cells, post-preservation viability remained high, and no cell death or cytoskeletal disruption was observed. This supercooling preservation method has the potential to serve as a practical strategy for the temporary storage of MPS. Full article
(This article belongs to the Special Issue Recent Advances in Microfluidics and Organoids for Biomedical Applications)
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30 pages, 20209 KB  
Article
Development of a Breast-on-a-Chip Microfluidic Model to Assess the Effect of Palbociclib in MCF-7 and T47D Cancer Cells
by Ingrid Larissa Melo Souza, Ana Cláudia Martins Braga Gomes Torres, Rodrigo Lucas, Isabella Gizzi Jiacomini, Sthefanie Ribas Klein, Maíra Barbosa e Reis, Andréia Akemi Suzukawa, Dalila Lucíola Zanette, Mateus Nóbrega Aoki, Alessandra Melo de Aguiar, Bruno Dallagiovanna and Lucas Blanes
Cells 2026, 15(5), 446; https://doi.org/10.3390/cells15050446 - 2 Mar 2026
Viewed by 1516
Abstract
Organ-on-a-chip devices combine microfabrication, tissue engineering, and microfluidics to recreate physiologically relevant microenvironments for in vitro studies. In this work, we validated a dynamic 2D breast-on-a-chip microfluidic bioassay operated at a controlled infusion rate of 20 µL/h to assess anticancer drug responses under [...] Read more.
Organ-on-a-chip devices combine microfabrication, tissue engineering, and microfluidics to recreate physiologically relevant microenvironments for in vitro studies. In this work, we validated a dynamic 2D breast-on-a-chip microfluidic bioassay operated at a controlled infusion rate of 20 µL/h to assess anticancer drug responses under defined flow conditions. Using Palbociclib as a reference compound, we evaluated proliferation, viability/apoptosis, cytoskeleton organization, and differential processing of the resistance-associated marker PARP1 in MCF-7 and T47D breast cancer cells. Under dynamic microfluidic conditions, Palbociclib induced dose-dependent effects, with the higher concentration (20 µM) consistently reducing cell proliferation and viability and increasing late apoptosis compared to 10 µM Palbociclib. Cytoskeletal disorganization was observed at both concentrations, while differential PARP1 processing patterns between MCF-7 and T47D cells were detected across doses. These responses are consistent with known effects of CDK4/6 inhibition and were reproducibly captured under controlled flow conditions. Overall, our results demonstrate that this breast-on-a-chip microfluidic model provides a reproducible and physiologically relevant in vitro platform for integrated assessment of drug efficacy and resistance-associated markers under dynamic perfusion. Full article
(This article belongs to the Special Issue Recent Advances in Microfluidics and Organoids for Biomedical Applications)
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25 pages, 3301 KB  
Article
Three-Dimensional Human Liver Micro Organoids and Bone Co-Culture Mimics Alcohol-Induced BMP Dysregulation and Bone Remodeling Defects
by Yuxuan Xin, Guanqiao Chen, Mohammad Majd Hammour, Xiang Gao, Fabian Springer, Elke Maurer, Andreas K. Nüssler and Romina H. Aspera-Werz
Cells 2026, 15(3), 274; https://doi.org/10.3390/cells15030274 - 1 Feb 2026
Viewed by 1766
Abstract
Hepatic osteodystrophy (HOD) is a frequent complication of chronic liver disease, marked by impaired osteogenesis and elevated fracture risk, particularly under sustained alcohol exposure. Bone morphogenetic proteins (BMPs), which play a crucial role in maintaining bone homeostasis, are dysregulated in alcoholic liver disease. [...] Read more.
Hepatic osteodystrophy (HOD) is a frequent complication of chronic liver disease, marked by impaired osteogenesis and elevated fracture risk, particularly under sustained alcohol exposure. Bone morphogenetic proteins (BMPs), which play a crucial role in maintaining bone homeostasis, are dysregulated in alcoholic liver disease. Specifically, decreased BMP2 and increased BMP13 have been linked to impaired osteogenesis and cartilage-like shifts in bone progenitors. A human in vitro system that recapitulates this hepatic BMP imbalance is needed to dissect mechanisms and identify targets. To address this, we established a long-term human three-dimensional liver–bone co-culture model that integrates hepatocytes (HepaRG), hepatic stellate cells (LX-2), and human umbilical vein endothelial cells (HUVECs) with bone scaffolds seeded with osteoblast precursors (SCP-1) and osteoclast precursors (THP-1). This study aimed to characterize the effects of chronic 50 mM alcohol exposure on hepatic fibrogenic activation and BMP ligand secretion, and to investigate the associated BMP-responsive signaling involved in bone cell lineage differentiation and functional activity. The results demonstrated alcohol-induced hepatic CYP2E1 activation and fibrogenic remodeling with EMT signatures, as well as a decrease in BMP2 and an increase in BMP13, without affecting BMP9. Liver-derived factors activated both canonical and non-canonical BMP signaling in bone progenitors, reduced osteoblast activity and mineralization, preserved osteoclast TRAP activity, and shifted the lineage toward chondrogenesis (SOX9↑, RUNX2↓). Notably, this BMP profile and skeletal phenotype reflect clinical observations in chronic liver disease, indicating that the model recapitulates key in vivo pathological features. This human liver micro-organoid co-culture reproduces alcohol-induced hepatic BMP dysregulation and downstream bone defects, offering an organoid-centric, microengineered platform for mechanistic studies and BMP-targeted therapeutic screening in HOD. Full article
(This article belongs to the Special Issue Recent Advances in Microfluidics and Organoids for Biomedical Applications)
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Review

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18 pages, 7648 KB  
Review
What Is the Current State of Stem Cell Therapy in Diabetes?
by Estera Bakinowska, Wojciech Jerzy Biniek, Kajetan Kiełbowski, Kamil Dyrka, Konrad Szewczyk, Hanna Ostałowska, Zuzanna Leciej and Andrzej Pawlik
Cells 2026, 15(10), 907; https://doi.org/10.3390/cells15100907 - 15 May 2026
Viewed by 1223
Abstract
Diabetes mellitus is a chronic and progressive metabolic disorder associated with abnormal blood glucose levels. The term involves several diseases with different pathophysiology mechanisms and treatment strategies. Stem cell-based treatments represent an emerging strategy for patients with diabetes mellitus with severe pancreatic insufficiency [...] Read more.
Diabetes mellitus is a chronic and progressive metabolic disorder associated with abnormal blood glucose levels. The term involves several diseases with different pathophysiology mechanisms and treatment strategies. Stem cell-based treatments represent an emerging strategy for patients with diabetes mellitus with severe pancreatic insufficiency and poor glycemic control. Over the last 20 years, researchers have investigated mesenchymal stem cell infusion and the transplantation of stem cell-derived β cells and islet tissues. This review aims to comprehensively discuss the latest advances in the field of stem cell use in diabetes, including clinical studies and preclinical experiments aiming at improving the efficacy and safety of stem cell use. Full article
(This article belongs to the Special Issue Recent Advances in Microfluidics and Organoids for Biomedical Applications)
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23 pages, 3502 KB  
Review
Modeling Drug and Radiation Resistance with Patient-Derived Organoids: Recent Progress, Unmet Needs, and Future Directions for Lung Cancer
by Dahye Lee, Yoonjoo Kim, Da Hyun Kang and Chaeuk Chung
Cells 2025, 14(24), 1994; https://doi.org/10.3390/cells14241994 - 15 Dec 2025
Cited by 8 | Viewed by 1989
Abstract
Background: Chemotherapy, targeted therapy and radiotherapy are the cornerstones of cancer treatment. However, therapeutic resistance—not only to these classic modalities but also to novel therapeutics like immune checkpoint inhibitors (ICIs) and antibody-drug conjugates—remains a major hurdle. Resistance significantly limits efficacy and increases recurrence [...] Read more.
Background: Chemotherapy, targeted therapy and radiotherapy are the cornerstones of cancer treatment. However, therapeutic resistance—not only to these classic modalities but also to novel therapeutics like immune checkpoint inhibitors (ICIs) and antibody-drug conjugates—remains a major hurdle. Resistance significantly limits efficacy and increases recurrence rates. A deep understanding of the molecular mechanisms driving this resistance is critical for developing personalized therapeutic strategies and improving patient outcomes. Recent Advances: Patient-derived cancer organoids have emerged as a powerful preclinical platform that faithfully recapitulates the genetic, phenotypic, and histological characteristics of original tumors. Consequently, PDOs are being widely utilized to evaluate drug responses, investigate resistance mechanisms, and discover novel therapeutic targets for a range of therapies. Limitations: While organoid models have been instrumental in studying resistance, significant limitations persist. First, standard organoid-only models lack key tumor microenvironment components, such as immune cells, limiting immunotherapy research. Second, there is a significant lack of research on acquired resistance, particularly in lung cancer. This gap is largely driven by the clinical infeasibility of rebiopsy in patients with progressive diseases. Third, the absence of standardized protocols for generating and validating resistance models hinders reproducibility and complicates clinical translation. Conclusions: This review summarizes recent advances in using organoid models to study resistance to chemotherapy, radiotherapy, and novel therapeutics (ICIs and ADCs). We emphasize the critical need for standardization in resistance organoid research. We also propose future directions to overcome existing challenges, including the integration of co-culture systems (to include the TME) and advanced technologies (e.g., scRNA-seq, Spatial Transcriptomics). Our specific focus is on advancing lung cancer resistance modeling to enable functional precision medicine. Full article
(This article belongs to the Special Issue Recent Advances in Microfluidics and Organoids for Biomedical Applications)
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38 pages, 10496 KB  
Review
Microfluidic-Based Scratch Assays for Wound Healing Studies: A Systematic Review
by Fernando A. Oliveira, Nicole M. E. Valle, Keithy F. da Silva, Arielly H. Alves, Marta C. S. Galanciak, Gabriel M. Rosário, Javier B. Mamani, Mariana P. Nucci and Lionel F. Gamarra
Cells 2025, 14(24), 1931; https://doi.org/10.3390/cells14241931 - 5 Dec 2025
Cited by 3 | Viewed by 2437
Abstract
Cell migration plays a central role in physiological processes such as wound healing, tissue regeneration, and immune responses, as well as in pathological conditions like chronic inflammation and tumor metastasis. Among the in vitro approaches to study this phenomenon, the conventional wound healing [...] Read more.
Cell migration plays a central role in physiological processes such as wound healing, tissue regeneration, and immune responses, as well as in pathological conditions like chronic inflammation and tumor metastasis. Among the in vitro approaches to study this phenomenon, the conventional wound healing assay (scratch assay) has been widely used due to its simplicity and low cost. However, its limitations, including poor reproducibility, damage to the extracellular matrix (ECM), and lack of dynamic physiological conditions, have prompted the development of microfluidic alternatives. Scratch-on-a-chip platforms integrate engineering and microtechnology to provide standardized, non-destructive methods for wound generation, preserve ECM integrity, and allow precise control of the cellular microenvironment. These systems also enable miniaturization, reducing reagent and cell consumption, while facilitating the application of biochemical or physical stimuli and real-time monitoring. This review synthesizes advances reported in the literature, addressing the different wound induction strategies (enzymatic depletion, physical depletion, and physical exclusion), the role of ECM composition, and the impact of mechanical forces such as shear stress. Overall, scratch-on-a-chip assays emerge as promising tools that enhance reproducibility, better mimic in vivo conditions, and broaden applications for therapeutic testing and mechanistic studies in cell migration. Full article
(This article belongs to the Special Issue Recent Advances in Microfluidics and Organoids for Biomedical Applications)
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