Hydrogels based on modified pectins capable of modulating neural cell behavior as prospective biomaterials in glioblastoma treatment

Abstract

Glioblastoma is the most common malignant tumor of the brain, but its treatment outcomes can be improved by new therapeutic techniques using biocompatible materials. Utilizing controllable alkaline de-esterification we obtained pectin preparation with 27.4% esterification degree and used it for bio-artificial matrix production. We discovered optimal gelation conditions in the presence of Ca²⁺ by the analysis of visco-elastic properties of the gels and produced a series of biomaterials in hydrogel forms. Hydrogels based on low-esterified pectin significantly slow down the metabolism of C6 glioma cells and neural stem cells (NSCs) and slightly decrease the viability of the C6 glioma, but not of NSCs. This happens due to a decrease in cell proliferation rate, while apoptosis degrees remain stable or negligibly decrease. We created a set of pectin hydrogels supplemented with different ratios of two ECM proteins-collagens I and IV. We have shown that the formation of cell processes in glioma C6 can be regulated by varying the ratio of two ECM proteins in gels used for 3D cell cultivation. Thus, composite matrix materials obtained can be used for modeling brain tumor invasion. The results presented suggest that modified pectins supplemented with two collagen types may serve as prospective biomaterials for glioblastoma treatment due to their ability to regulate glioma cell dynamics.

Keywords: Bio-artificial matrix; Biocompatible materials; Glioma cells; Neural stem cells; Neurite outgrowth; Polysaccharide; Scaffold; Viscoelastic properties.