Hydrogels of tremendous interest in the field of biomedical materials as extracellular matrix substitute.[1] One of the main challenges in regenerative medicine is to synthesize scaffolds in which cells will be able to proliferate, differentiate and behave like in their natural environment. Hydrogels made from natural biopolymers such as collagen or hyaluronic acid, or complex extracellular matrix extracts (MatrigelTM), are inherently biocompatible and bioactive. However, they present several drawbacks such as a high cost of production, a weak batch-to-batch reproducibility, a potential microbial contamination during the isolation process, and risks of immunogenicity.
In this context, we envisioned a novel type of cross-linked biomimetic hydrogels built in a fully modular and bottom-up approach. This strategy is based on the synthesis of various hybrid blocks, containing one or several alkoxysilyl moieties,[2] that can be combined and engaged in a sol-gel process to yield multifunctional hydrogels. Upon hydrolysis and condensation of silyl precursors, a covalent bio-inorganic tridimensional network is formed.
The selected units (e.g. peptide sequence derived from collagen, bioactive peptide ligands such as RGD, fluorophores, PEG…) are mixed in a desired ratio and dissolved in physiological aqueous buffers. The different solutions turned quickly into covalent functional gels at 37°C. Interestingly, the sol-gel reaction proceeds chemoselectively and enable the inclusion of fragile biomolecules and even the embedment of cells. We demonstrated that these hydrogels exhibited biological properties depending on the nature of the hybrid bioactive peptide introduced, promoting cell adhesion or displaying antibacterial activity.[3] Interestingly, the speed of polymerization (and the resulting viscosity of the solution) can be controlled by temperature or catalysts and liquid hybrid solution can be used to 3D-print functional scaffolds[4]. At last, we demonstrated that mesenchymal stem cells could be embedded in such hybrid-peptide hydrogels[5], opening the way to biofabrication of scaffolds for tissue engineering.