3D printing of biocompatible low molecular weight gels: Imbricated structures with sacrificial and persistent N-alkyl-d-galactonamides.

HYPOTHESIS: We have shown earlier that low molecular weight gels based on N-heptyl-d-galactonamide hydrogels can be 3D printed by solvent exchange, but they tend to dissolve in the printing bath. We wanted to explore the printing of less soluble N-alkyl-d-galactonamides with longer alkyl chains. Less soluble hydrogels could be good candidates as cell culture scaffolds. EXPERIMENTS: N-hexyl, N-octyl and N-nonyl-d-galactonamide solutions in dimethylsulfoxide are injected in a bath of water following patterns driven by a 2D drawing robot coupled to a z-platform. Solubilization of the gels with time has been determined and solubility of the gelators has been measured by NMR. Imbricated structures have been built with N-nonyl-d-galactonamide as a persistent ink and N-hexyl or N-heptyl-d-galactonamide as sacrificial inks. Human mesenchymal stem cells have been cultured on N-nonyl-d-galactonamide hydrogels prepared by cooling or by 3D printing. FINDINGS: The conditions for printing well-resolved 3D patterns have been determined for the three gelators. In imbricated structures, the solubilization of N-hexyl or N-heptyl-d-galactonamide occurred after a few hours or days and gave channels. Human mesenchymal stem cells grown on N-nonyl-d-galactonamide hydrogels prepared by heating-cooling, which are stable and have a fibrillar microstructure, developed properly. 3D printed hydrogels, which microstructure is made of micrometric flakes, appeared too fragile to withstand cell growth.

Wet spinning of a library of carbohydrate low molecular weight gels.

HYPOTHESIS: Recently, a low molecular weight hydrogel based on a carbohydrate alkyl amide has been successfully used as biomaterial for neuron cell culture and for 3D printing. Varying the molecular structure should make it possible to extend the library of carbohydrate low molecular weight hydrogels available for these applications and to improve their performances. EXPERIMENTS: Thirteen molecules easy to synthetize and designed to be potentially biocompatible were prepared. They are based on gluconamide, glucoheptonamide, galactonamide, glucamide, aliphatic chains and glycine. Their gelation in water was investigated in thermal conditions and wet spinning conditions, namely by dimethylsulfoxide-water exchange under injection. FINDINGS: Nine molecules give hydrogels in thermal conditions. By wet spinning, six molecules self-assemble fast enough, within few seconds, to form continous hydrogel filaments. Therefore, the method enables to shape by injection these mechanically fragile hydrogels, notably in the perspective of 3D printing. Depending on the molecular structure, persistent or soluble gel filaments are obtained. The microstructures are varied, featuring entangled ribbons, platelets or particles. In thermal gelation, molecules with a symmetrical polar head (galacto, glucoheptono) give flat ribbons and molecules with an asymmetrical polar head (gluco) give helical ribbons. The introduction of an extra glycine linker disturbs this trend.