In the proposed 3D models the significant upregulation of genes OCT-4, NANOG and SOX-2, typically used as stemness markers due to their essentiality in preserving the pluripotency and the self-renewal property of cancer stem cells36,61–64 , demonstrated that the presence of 3D biomimetic scaffold, reproducing the nanostructure and physico-chemical features of native environment, induces the higher stem phenotype in 3D sarcospheres compared to those grown without scaffolds (Fig. 7a,b). This evidence concerns the gene NANOG and cancer.