LabCom_2022 - V2 - Laboratoires communs organismes de recherche publics – PME/ETI - Edition 2022 - Vague 2

Immunocompetence and vascularisation for a skin-on-a-chip model. – INCREASE

Submission summary

Every year, 115 million animals are used worldwide for basic research, toxicological evaluation of chemicals, drugs, pesticides, biocides and medical devices (MD). The ethical and regulatory context encourages the limitation of animal experimentation in these fields. Concerning MDs, the protection of patients against potential biological risks is a requirement to which manufacturers and economic operators in Europe are subject (MDR 2017/745).
The recent publication of ISO 10993-23:2021, which incorporates the 3Rs principle (Replacement, Reduction, Refinement; Directive 2010/63/EU), offers evaluators the possibility of studying the biocompatibility of MDs using alternative approaches in order to limit testing on animal models. However, although several reconstructed human epidermis models have been approved for testing skin irritation by chemicals, only SkinEthic® (SkinEthics, France) and EpiDerm® (MatTek, USA) are validated for solid MD extracts. Even if these models are advantageous compared to 2D in vitro models (epidermis morphology, lipid composition, biochemical markers), the absence of immune and endothelial cells prevents from reproducing all functions of the skin, and in particular from predicting the key events likely to induce a sensitization (allergy).
The acquisition of 3D skin models integrating a greater variety of cell types and a structure closer to physiology has a triple purpose for ICARE: 1) ethical, by proposing alternative methods of toxicological evaluation in accordance with the 3Rs principle, 2) physiological, in order to mimic as closely as possible the tissue under consideration, 3) commercial, because the turnover will be increased not only by a consolidation of the MD biocompatibility market, but also by an opening up to evaluations in cosmetics and dermo-cosmetics
The INCREASE Joint Laboratory will associate the SME ICARE (Saint-Beauzire), European leader in the control of health products safety for more than 25 years, with the team of Dr. Vincent Flacher from the I2CT Laboratory (Strasbourg), which has a scientific expertise in the construction of skin models displaying different combinations of immune, endothelial cells and/or sensory neurons. These models constitute an in vitro analysis system mimicking physiology very closely and represent a major asset to screen and quantify precisely the probability that a molecule induces a sensitization reaction. The LabCom will provide I2CT with the means to obtain regulatory validation and standardization of complex 3D cultures and their integration in microfluidic chips.
INCREASE's ambition is to adapt these skin models to the requirements of MD toxicological evaluations and cosmetic compounds screening. Based on the expertise of I2CT (immunology, dermatology, 3D models) and ICARE (toxicology, regulation), the LabCom will focus on the following axes:
1) Comparison of the predictive capacity of a skin model including immune and endothelial cells from healthy donors with that of reference in vivo and in vitro models for MD and chemicals;
2) Development of skin models whose structure, immunocompetence and endothelial network are derived from characterized human cell lines;
3) Integration of the skin model into a microfluidic culture-on-chip system, facilitating the sampling of soluble secretions and migrating immune cells and comparison with reference models for MD and chemicals.
The LabCom INCREASE will establish a perennial collaborative structure associating ICARE and I2CT and dedicated to the development of reliable and innovative skin models on chip.

Project coordination

Vincent FLACHER (Immunologie Immunopathologie et Chimie Thérapeutique (UPR 3572))

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

I2CT Immunologie Immunopathologie et Chimie Thérapeutique (UPR 3572)
ICARE Laboratoire ICARE

Help of the ANR 363,000 euros
Beginning and duration of the scientific project: March 2023 - 54 Months

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