In Vitro Contact Guidance of Glioblastoma Cells on Metallic Biomaterials

Abstract

Cancer cells' ability to sense their microenvironment and interpret these signals for the regulation of directional adhesion plays crucial role in cancer invasion. Furthermore, given the established influence of mechanical properties of the substrate on cell behavior, the present study aims to elucidate the relationship between the contact guidance of glioblastoma cell (GBM) and evolution of microstructural and mechanical properties of the implants. SEM analyses of the specimens subjected to 5 and 25% of plastic strains revealed directional groove-like structures in micro and submicro-sizes, respectively. Microscale cytoplasmic protrusions of GBMs showed elongation favored along the grooves created via deformation markings on 5% deformed sample. Whereas filopodia, submicro-sized protrusions facilitating cancer invasion, elongated in the direction perpendicular to the deformation markings on the 25% deformed sample, which might lead to easy and rapid retraction. Furthermore, number of cell attachment was 1.7-fold greater on 25% deformed sample, where these cells showed the greatest cellular aspect ratio. The directional attachment and contact guidance of GBMs was reported for the first time on metallic implants and these findings propose the idea that GBM response could be regulated by controlling the spacing of the deformation markings, namely the degree of plastic deformation. These findings can be applied in the design of cell-instructive implants for therapeutic purposes to suppress cancer dissemination.