Hybrid 2D polymeric–ceramic biosupports are fabricated by mixing a nanostructured CeO2 powder with 85:15 poly(D,L-lactic-co-glycolic acid) (PLGA)/dichloromethane solutions at specific concentrations, followed by solvent casting onto pre-patterned molds. The mold patterning allows the orientation of ceramic nanoparticles into parallel lines within the composite scaffold. The ability of the produced films to host and address cell growth is evaluated after 1, 3, and 6 days of culturing with murine derived cardiac and mesenchymal stem cells (CSCs and MSCs), and compared with PLGA films without ceramics and loaded with nanostructured TiO2. Aligned cell growth is observed only for scaffolds that incorporate oriented ceramic nanoparticles, attributed to the nanoceramic ability to modulate the roughness pitch, thus improving cell sensitivity towards the host surface features. Better CSC and MSC proliferative activity is observed for CeO2 composites with respect to either TiO2-added or unfilled PLGA films. This evidence may be related to the nanostructured CeO2 antioxidative properties.