Summary
3D organoids and tumoroids derived from patient cells have emerged as a powerful alternative to 2D cultures and animal testing. Because cell-matrix interactions are crucial for survival, proliferation, and migration, the choice of biomaterial heavily dictates the functionality of these in vitro models. However, oncology research is currently bottlenecked by a lack of well-defined, animal-free biomaterials whose mechanical and chemical properties can be modulated with high reproducibility.
To overcome this challenge, our multidisciplinary consortium of chemists, biologists, and clinicians proposes to design highly defined culture matrices using recombinant collagen. By utilizing a non-animal, bio-synthetic source, we bypass the batch-to-batch variability of traditional materials. The goal is to develop tailored hydrogels to support the growth of colorectal epithelial organoids (from adult cells) and bronchial epithelial organoids (from iPSCs) to study tumor initiation mechanisms under inflammatory conditions. We will synthesize silylated collagen hydrogels by functionalizing collagen with alkoxysilane groups and covalently cross-linking them through a mild sol–gel process carried out under physiological conditions and temperature. This non-toxic, bioorthogonal, and chemoselective reaction enables the creation of customizable mechanical properties and biochemical environments.

The Consortium
This project bridges chemistry and advanced biology across three specialized teams:

1. Peptides Team (IBMM, Montpellier): Experts in bio-inspired precursors and sol-gel chemistry to build biomimetic extracellular matrices.
2. Audrey Ferrand’s Team (IRSD, Toulouse): Specialists in colorectal cancer initiation and advanced “colon-on-a-chip” models.
3. Pr. John De Vos’s Team (IRMB, Montpellier): Developers of fully functional, patient-derived bronchial epithelium models from iPSCs.