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

Abstract

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.

A Collagen-Mimetic Organic-Inorganic Hydrogel for Cartilage Engineering

“…By contrast, we developed here a biocompatible nucleophile catalytic system consisting of a low concentration of NaF (0.1 mg/mL) combined with glycine (10 mg/mL). We have already demonstrated this catalytic effect on PEG hydrogels [ 48 ] and HMPC alike [ 27 ]. We applied these experimental conditions to obtain the hybrid collagen peptide hydrogels.…”

“…The gelation of the hybrid collagen-like peptide solution was obtained by a sol-gel process by the concomitant hydrolysis of ethoxysilyl moieties into hydroxysilyl moieties and condensation into siloxane bonds, creating reticulation nodes [ 48 ]. In numerous biomaterial applications, sol-gel is either acid- or base-catalyzed and does not allow the entrapment of cells before a careful neutralization.…”

Encapsulation of BSA in hybrid PEG hydrogels: stability and controlled release

“…8,[13][14][15][16][17][18] A new family of biocompatible hybrid functional hydrogels polymers, have emerged recently that can cross-link with stable chemical bonds, namely siloxane, Si-O-Si. [19][20][21][22] It is dened by the coexistence of organic (e.g. polymers, peptides, amino acids, etc.)…”

“…Inorganic sol-gel polymerization leads to hybrid hydrogels useful for the preparation of water-containing materials, 20 allowing the inclusion of water soluble bioorganic molecules. 19,[22][23][24] Hydrolysis of alkoxysilane (e.g. triethoxysilane, -Si(OC 2 H 5 ) 3 ) can be triggered in acidic conditions, the subsequent condensation being obtained during neutralisation, giving rise to three-dimensional network siloxane bonds (Si-O-Si).…”

“…triethoxysilane, -Si(OC 2 H 5 ) 3 ) can be triggered in acidic conditions, the subsequent condensation being obtained during neutralisation, giving rise to three-dimensional network siloxane bonds (Si-O-Si). Interestingly, both reactions can also be catalysed in physiological conditions 22 allowing the preparation of bio inks and the 3D bio printing of living cells. 21,25 It seemed obvious that the versatility of the sol-gel reaction and the ease to modulate the hydrogel network composition by adding other molecules or functions aer silylation (e.g.…”