Accepted_test

Central nervous system characterized by the specific extracellular matrix regulating cell behavior in normal and diseased tissues via modulation of specific proteins and glycopolymers content generally demonstrating most glycosylated matrix variant among the variety of ECM subtypes. Crucial ECM transformations occur in structurally damaged CNS or during carcinogenesis typically resulting in matrix fibrosis and increasing protein-to-carbohydrates ratio. New therapeutic strategies could be developed using implantable composite biomaterials aiming ECM remodeling in diseased neural tissues.

We have elaborated a series of biomaterials based on modified polysaccharides varied in ionogenic group content supplemented with ECM proteins that seem to be promising for treatment of CNS injury and brain tumors. To establish cell-based and animal models helping to develop new kinds of neurotropic therapeutics, CRISPR/Cas gene editing and transgenic manipulations were done that help us to produce a number of cell lines of glioma cells characterizing by specific molecular profiles and bearing particular reporter systems. Cells with different mutational status in TP53 and IDH1 genes as well as bearing constructs with HIF1alpha inducible hypoxia factor were produced and 3D models with biomaterials developed help us to investigate cell migration and invasiveness in different matrix subtypes. Functional tests on cell-based and animal models together with transcriptomic analysis showed the mechanisms of actions of biomaterials produced and found particular compositions as more advantages for brain cancer therapy or matrix remodeling for neural regeneration.

This work was supported by Russian Science Foundation (RSF) grant 20-15-00378.