Innervated Epidermis.

The Challenge.

The skin is a protective organ, able to decode a wide range of tactile, thermal, or noxious stimuli. Psoriasis, atopic dermatitis, eczema, wound healing, skin irritation, herpes infection, hyperhidrosis, neuropathy, and skin sensitivity syndrome are conditions involving both skin cells, i.e., keratinocytes and neurons. Preclinical research is limited by in vitro models, which are not always relevant either because they often use rodent neurons cells or because the cocultures of skin cells and neurons do not fully recapitulate the anatomical structure, i.e. , a neuronal cell body compartmentalized from the skin. ​

The Solution.

The association between compartmentalized microfluidic device technology and human-derived sensory neurons may address these limitations. The interest in this model is to (i) apply a stimulus on the skin and evaluate the impact on neurons or (ii) apply a stimulus on neurons and evaluate the impact on the skin.

DuaLink NeuroFluidics Devices & Skin NeuroFluidics Cultures
Primary keratinocytes in channel 3
hiPSC-derived sensory neurons somas in channel 1 & extensions in channel 3
Compound response in channel 3

Using organs-on-chip to screen compounds effect on an innervated epidermis model.

This Use Case shows that, by using neurons as bio-digital sensors, the electrical effects of a compound applied to the healthy skin compartment can be recorded on neurons. This opens the way to screening compounds on altered models (sensitive skin, atopic dermatosis...).

Evaluation of the effect on neuron electrical activity following treatment
Acute and « chronic »activity modulation
Comparison with compounds of reference

Test your compound on our ready-to-use NeuroFluidics Cultures with reference compound already on the market or having failed in the clinical phase.

Benefits.

Cosmetic Regulation​

Cosmetic regulation ensures product safety, labeling accuracy, and adherence to quality standards in the beauty industry.
No animal testing
Drug and cosmetic efficacy and toxicity
Compatible with standard analytical method and tools

Compartmentalization

Compartmentalized microfluidics devices to recreate skin compartment and neurons or endothelial cells compartment.​
Discrimination of mode and mechanism of action
Pathophysiological applications (sensitive skin and pruritus, inflammatory dermatosis…)

Fully Compatible

NeoBento™, the standard SBS format for NeuroFluidics Devices for readouts and lab equipments compatibility.
Pump-free & expensive equipment-free
Standard equipment compatibility
Electrophysiology, imaging and biochimic analysisreadouts compatibility

PDMS Optically Transparent

Soft silicon material, optically transparent for microscopy compatiblity and porous gas permability
Imaging (Immunofluorescence, Calcium Imaging…)
Confocal Imaging
Perfusion-free with high biocompatibility

Our Offers.

NETRI Services.

Technological Transfert
FTE & Screening Services
Co-development
Analytical Services

NETRI Products.

NeuroFluidics Devices
NeuroFluidics Cultures
NeuroFluidics Digital
Training & Organs-on-chip Kits

Summary.

Guichard, A., Remoué, N., & Honegger, T. (2022). In vitro sensitive skin models: review of the standard methods and introduction to a new disruptive technology. Cosmetics, 9(4), 67. https://doi.org/10.3390/cosmetics9040067
Maisonneuve, B. G. C., Vieira, J., Larramendy, F., & Honegger, T. (2021). Microchannel patterning strategies for in vitro structural connectivity modulation of neural networks. BioRxiv, 2021-03. https://doi.org/10.1101/2021.03.05.434080
Castiglione, H., Vigneron, P. A., Baquerre, C., Yates, F., Rontard, J., & Honegger, T. (2022). Human Brain Organoids-on-Chip: Advances, Challenges, and Perspectives for Preclinical Applications. Pharmaceutics, 14(11), 2301. https://doi.org/10.3390/pharmaceutics14112301​
Gabriel-Segard, T.; Rontard, J.; Miny, L.; Dubuisson, L.; Batut, A.; Debis, D.; Gleyzes, M.; François, F.; Larramendy, F.; Soriano, A.; et al. (2023). Proof-of-Concept Human Organ-on-Chip Study: First Step of Platform to Assess Neuro-Immunological Communication Involved in Inflammatory Bowel Diseases. Int. J. Mol. Sci., 24, 10568. https://doi.org/10.3390/ijms241310568
Rontard J, Maisonneuve BGC, Honegger T. (2023). Expanding human-based predictive models capabilities using organs-on-chip: A standardized framework to transfer and co-culture human iPSCs into microfluidic devices. Arch Pharm Pharma Sci. ; 7: 017-021. https://doi.org/10.29328/journal.apps.1001039
Fuchs, Q., Batut, A., Gleyzes, M., Rontard, J., Miny, L., Libralato, M., Vieira, J., Debis, D., Larramendy, F., Honegger, T., Messe, M., Pierrevelcin, M., Lhermitte, B., Dontenwill, M., Entz-Werlé, N. (2021). Co-culture of Glutamatergic Neurons and Pediatric High-Grade Glioma Cells Into Microfluidic Devices to Assess Electrical Interactions. J. Vis. Exp. (177), e62748, https://doi.org/10.3791/62748
[2023] Compartimentalized culture of primary or hiPSC-derived neurons using an MEA-capable high-throughput organs-on-chip platform
[2022] The DuaLink Chips how to improve reproducibility in compartmentalized co-cultures
DuaLink Protocol
DuaLink MEA Protocol
Sensory Neurons Protocol
Sensory Neurons MEA Protocol
Fixation & Immunostaining Protocol
Sensory Neurons
Primary Keratinocytes
Electrophysiology
Immunofluorescence
Live Dead Assays

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