Organ-on-a-Chip Models—New Possibilities in Experimental Science and Disease Modeling
Abstract
:1. Introduction
2. Organ-on-a-Chip Technology
2.1. Technical Aspects of the OOC Models’ Design
2.2. Biological Aspects of OOC Model Design
3. OOC Models in Neurosciences
3.1. Blood–-Brain Barrier-on-a-Chip
3.2. Brain–Gut–Microbiota Axis-on-a-Chip
3.3. Amyotrophic Lateral Sclerosis-on-a-Chip
3.4. Parkinson’s Disease-on-a-Chip
4. The Introduction of the OOC Technology in Experimental Neuroendocrinology
5. Benefits and Limitations of the OOC Technology
6. Future Direction of the OOC Technology in Neurosciences
7. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Material | Advantages | Disadvantages | References |
---|---|---|---|
Poly(dimethylsiloxane) (PDMS) | Flexibility and cost-effectiveness, ease of fabrication, biocompatibility | Absorption of small molecules, leakage issues | [41] |
Silicon glass | Precision and robustness, optical clarity, chemical compatibility | High fabrication cost, limited reusability, complex fabrication process | [42] |
Thermoplastics | High optical transparency, solvent resistance, low gas permeability | Relatively high rigidity, complex manufacturing process, limited compatibility with certain photomaterials | [44,45] |
Epoxy resins and adhesives | Advantageous mechanical properties, ability to integrate multiple sensors and actuators, hydrophilicity | Challenges with turning it hydrophobic, leakage issues | [46,47,48] |
Thermoplastics combined with hydrogels or elastomers | Hydrogels: soft mechanical properties closely mimic native tissue, biocompatible microenvironment provides improves cell viability Polyurethane elastomers: optical transparency and biocompatibility, strong bonding capabilities | Hydrogels: swelling issues, challenging process of bonding with filters; Polyurethane elastomers: cytotoxic concerns, lower gas permeability than PDMS, processing challenges regarding degassing and molding | [49,50,51] |
Organ/Structure Replicated | Disease/Condition Addressed | Cells/Tissues Used | Main Findings | Reference |
---|---|---|---|---|
Blood–brain barrier (BBB) | Drug discovery related to the BBB | Brain capillary-like endothelial cells (BCLECs) derived from human-induced pluripotent stem cells (hiPSCs) | A two-step differentiation protocol to derive BCLECs from hiPSCs, demonstrating that the combination of VEGF, Wnt3a, and retinoic acid significantly improved the expression of endothelial markers and barrier properties, including transendothelial electrical resistance and paracellular permeability. The derived BCLECs exhibited moderate expression of P-glycoprotein and responded to inflammatory stimuli, indicating their potential for modeling BBB function in vitro | [65] |
BBB using the tissue chip platform “DigiTACK” | Neuroinflammation and related neurological disorders, with a focus on cytokine secretion dynamics | Primary mouse brain microvascular endothelial cells (mBMECs) | The DigiTACK platform enabled longitudinal monitoring of cytokine secretion from the mBMECs barrier, revealing significant differences in cytokine profiles between luminal and abluminal sides and demonstrating the potential for high-throughput analysis in studying CNS disease mechanisms | [66] |
A gut–brain axis chip that mimics the intestinal and neural environment | Alzheimer’s disease model to evaluate the effects of gut microbiota-derived metabolites and exosomes | hiPSCs differentiated into induced neural stem cells and Caco-2 cells | Metabolites and exosomes derived from gut microbiota influenced neural growth, maturation, and synaptic plasticity, suggesting their potential as therapeutic candidates for neurodevelopmental and neurodegenerative disorders | [67] |
A feto-maternal interface organ-on-chip (FMi-OOC) model | Ascending infections and their associated inflammatory responses that are significant risk factors for spontaneous preterm birth (PTB) | Primary human cells from the fetal membranes, including decidual cells, chorion trophoblasts, amnion mesenchymal cells, and epithelial cells | The FMi-OOC successfully demonstrated the propagation of lipopolysaccharide-induced inflammation from the maternal to fetal compartments, revealing distinct inflammatory cytokine profiles and highlighting the immune imbalance that can contribute to PTB. The model maintained key physiological characteristics of the in vivo environment, validating its utility for studying the feto-maternal interface | [68] |
A six-chamber vagina–cervix–decidua-organ-on-a-chip (VCD-OOC) model that mimics the female reproductive tract during pregnancy | Ascending Ureaplasma parvum infection and its association with PTB | Vaginal epithelial cells, cervical epithelial and stromal cells, and decidual cells, all derived from immortalized human cell lines | U. parvum infection did not cause significant cell death or massive inflammation in the VCD-OOC model. However, combined with lipopolysaccharides, it induced a substantial inflammatory response. In vivo studies showed that the vaginal inoculation of U. parvum alone resulted in low PTB rates, while intra-amniotic injection significantly increased PTB rates | [69] |
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Wysoczański, B.; Świątek, M.; Wójcik-Gładysz, A. Organ-on-a-Chip Models—New Possibilities in Experimental Science and Disease Modeling. Biomolecules 2024, 14, 1569. https://doi.org/10.3390/biom14121569
Wysoczański B, Świątek M, Wójcik-Gładysz A. Organ-on-a-Chip Models—New Possibilities in Experimental Science and Disease Modeling. Biomolecules. 2024; 14(12):1569. https://doi.org/10.3390/biom14121569
Chicago/Turabian StyleWysoczański, Bartłomiej, Marcin Świątek, and Anna Wójcik-Gładysz. 2024. "Organ-on-a-Chip Models—New Possibilities in Experimental Science and Disease Modeling" Biomolecules 14, no. 12: 1569. https://doi.org/10.3390/biom14121569
APA StyleWysoczański, B., Świątek, M., & Wójcik-Gładysz, A. (2024). Organ-on-a-Chip Models—New Possibilities in Experimental Science and Disease Modeling. Biomolecules, 14(12), 1569. https://doi.org/10.3390/biom14121569