Lineage‐Specific Commitment of Stem Cells with Organic and Graphene Oxide–Functionalized Nanofibers

Abstract Controlling the differentiation to certain lineages is the main goal of current stem cell research, which might exploit new routes based on the interaction of cells with nanomaterials. Here it is shown that primary neurospheres from dental pulp stem cells grown on combinatorial surfaces with different fibrous morphology and graphene oxide functionalization exhibit different differentiation propensity. The developed materials strongly influence the stem cell fate, as highlighted by morphological, immunofluorescence, molecular biology, and functional analyses. Instructive cues lead to the increased expression of markers that are characteristic of selective differentiation into osteoblasts, glial cells, fibroblasts, and neurons even in basal medium conditions, and randomly oriented fibers are found to revert neuronal precommitment and to trigger osteoblastic differentiation. Graphene oxide coatings lead instead to the relatively enhanced expression of genes typical of either glial or neuronal commitment, depending on the underlying nanofibrous morphology. The mechanisms addressing cell fate are investigated, highlighting the correlation of wetting anisotropy and protein adsorption capacity of different surfaces, ultimate cell conformational changes reflected by skeletal and nuclear elongation, and directed cell commitment. Cues from the different surfaces are therefore lineage‐specific, unveiling remarkable potentialities for cellular programming by means of nanomaterials.