Biomimetic 3D Materials for More Predictive Intestinal Toxicity Testing

Assessing the toxicity of chemical substances to human health requires reliable experimental models that accurately reflect human physiology. The intestine represents a major interface between the human body and its environment, yet current cellular models fail to fully reproduce its structural organization and physical properties. This PhD project aims to develop advanced intestinal models using three-dimensional biomimetic materials (BAM). Through 3D printing technologies, these materials will reproduce key architectural features of the intestine, including its crypts and villi. An innovative, patented coating, whose mechanical properties can be tuned independently of scaffold geometry, will mimic essential characteristics of the intestinal extracellular matrix. Intestinal organoid-derived cells will be cultured on these scaffolds to develop models that more closely resemble human intestinal physiology. The project will investigate how microenvironmental geometry and stiffness influence intestinal cell organization, differentiation, and function. The resulting models will then be exposed to reference chemicals with known toxicological effects. Cellular responses will be analyzed and compared with those obtained using conventional culture models. The objective is to determine whether better reproducing the intestinal microenvironment can improve the sensitivity, reproducibility, and physiological relevance of toxicity testing. This interdisciplinary project will combine biomaterials engineering, cell biology, mechanobiology, and toxicology. Ultimately, these advanced intestinal models could also contribute to reducing the reliance on animal experimentation.

3D Bio-Based mRNA-Enriched Materials for Bone Regeneration: Optimizing Osteogenic Differentiation Using AI-Based Methods

This PhD project aims to develop bioresorbable scaffolds functionalized with mRNA using a polycation, poly(L-lysine), and hyaluronic acid, arranged in different structural architectures.
The originality of this approach lies in two key aspects. First, these biomaterials will incorporate mRNA sequences encapsulated within nanoparticles, encoding proteins that play a crucial role in bone regeneration, such as VEGF (Vascular Endothelial Growth Factor) and BMP (Bone Morphogenetic Proteins). Second, the project will investigate how the three-dimensional organization of the polymer network influences the biological performance of the scaffold.
The overall objective is to transform cells located at the injury site into localized therapeutic protein factories through in situ transfection, enabling sustained, localized production of the therapeutic proteins at physiological concentrations.
Artificial intelligence (AI) approaches will be used as computer-aided design tools to analyze and exploit the experimental data. These methods will guide the optimization of scaffold design—including composition, architecture, and mRNA loading—to maximize osteogenic differentiation while reducing the number of experimental iterations required.
This work is part of an interdisciplinary and collaborative research project. The PhD candidate will also contribute to data analysis, the writing of scientific publications, and the dissemination of research findings at national and international conferences.