A ‘LEGO’-LIKE METHOD TO ACCESS MULTIFONCTIONAL HYDROGELS FOR MESENCHIMAL STEM CELL-BASED CARTILAGE REGENERATION – LEGOGEL

LEGOGEL is a multidisciplinary project built on the complementary expertise of three research teams specialized in the design of bioactive molecules (Partner 1 IBMM), the sol-gel inorganic chemistry and the design of functional hybrid materials (Partner 2, ICGM) and cell therapy strategies for osteo-articular diseases (IRMB, Partner 3). Legogel proposes a ground-breaking technology to obtain multifunctional hydrogels whose composition could mimic the complexity and the diversity of extracellular matrices. This is of high importance to design hydrogels suitable for cell-based therapies. The approach relies on the synthesis of original and patented ‘hybrid’ building blocks comprising a biomolecular moiety (peptide ligands for cell adhesion, differentiation factors, collagens, hyaluronic acid…) and one or several alkoxysilane groups whose position within the biomolecule is perfectly controlled. The hybrid blocks (i.e. the ‘lego’ parts) react together chemo selectively to form a hydrogel. This sol-gel process proceeds in water, at 37°C without any cross-linking reagent nor toxic chemical thus being fully compatible with the stability of biomolecule and the presence of cells.
The hydrogels prepared in the frame of Legogel are designed to tackle tissue engineering issues, in particular to promote cartilage regeneration. The hydrogel will induce targeted differentiation of mesenchymal stem cells (MSC) into chondrocytes.
The work program is organized in three workpackages.
The first workpackage is dedicated to the synthesis of hybrid blocks.
It includes hybrid biopolymers (hyaluronic acids and collagens) to form the backbone of the three dimensional biomimetic structure, bioactive peptides (e.g. peptides promoting cell adhesion, extracellular matrix production…) and contrast agents to visualize and to study the degradation of the gels.
The second workpackage concerns the preparation and the characterization of the hydrogels.
The materials will be optimized for their mechanical, structural and biological properties. The Legogel approach is highly versatile and any combination of hybrid block in appropriate concentrations can be used, to finely tune these properties. As an example, peptide sequence sensitive to enzymatic degradation can be introduced to modulate the degradability of the gels and to enable the controlled release of factors immobilized covalently in the gel. Interestingly, the mixture of bioorganic blocks as a liquid will allow their use in two different ways. On one hand, this solution could be used, turning into a gel after in vivo injection. On the other hand this solution can be used as a bio-ink to be 3D-printed for the bio fabrication of a porous scaffold. This scaffold will be used to treat full thickness cartilage lesion thanks to a multifunctional bilayer favoring the superimposed cartilage on bone formation.
The last workpackage deals with in vitro and in vivo study of MSC embedded in hydrogels.
MSC will be poured inside the liquid solution before gelation and the hydrogels or the imprinted scaffolds will be studied in vitro for their biocompatibility, biodegradability, and their chondro-s or osteo-inductive properties. At last, gels and scaffolds will be implanted in the mouse and the in vivo formation of neotissues will be controlled by immunohistological and RT-PCR analyses. Legogel project proposes a rupture technology to craft biomimetic gels. Universal, simple and avoiding the use a chemical reagents for reticulation and functionalization of gels, this method is likely to unlock numerous applications in the fields of cell therapy and tissue engineering.