Biocompatible Glycine-Assisted Catalysis of the Sol-Gel Process: Development of Cell-Embedded Hydrogels

The sol-gel process can be used for hydrogel cross-linking, thus opening an attractive route for the design of biocompatible hydrogels under soft conditions. The sol-gel process can be catalysed at basic or acidic pH values, under neutral conditions with the addition of a nucleophile. Therefore, working around pH 7 unlocks the possibility of direct cell embedment and the preparation of bioinks. We aimed to propose a generic method for sol-gel 3D bioprinting, and first screened different nucleophilic catalysts using bis-silylated polyethylene glycol (PEG) as a model hydrogel. A synergistic effect of glycine and NaF, used in low concentrations to avoid any toxicity, was observed. Biocompatibility of the approach was demonstrated by embedding primary mouse mesenchymal stem cells. The measure of viscosity as a function of time showed the impact of reaction parameters, such as temperature, complexity of the medium, pH and cell addition, on the kinetics of the sol-gel process, and allowed prediction of the gelation time.