Engineering shape-memory polymer microspheres as tunable curved surfaces for stem cell fate manipulation

Biomaterials mimic extracellular matrix (ECM) in tissue regeneration by providing essential physical and biochemical cues for stem cell growth; many studies have revealed the influence of such cues on stem cell fate. However, curved surfaces, the basic geometry of organisms, have rarely been considered. Besides, existing curved platforms generally offer only fixed, non-adjustable curvatures, hindering systematic investigation of their effects on stem cell fate. Here, we design and propose shape-memory polymer (SMP) microspheres as a tunable curved platform for culturing bone marrow stromal cells (BMSCs), a good candidate in tissue engineering owing to their self-renewal capacity and multi-lineage differentiation potential. After programming by controlling deformation strains, SMP microspheres transform into ellipsoidal shapes with different curvatures (aspect ratios), constructing tunable curved surfaces for BMSCs. Results indicate that BMSCs cultured on surfaces with larger curvature (smaller aspect ratio) undergo greater nuclear deformation, and vice versa. Furthermore, the curved surfaces provided by the microspheres enhance osteogenic differentiation more effectively than flat films; the larger the curvature (the smaller the aspect ratio), the stronger the promoting effect on osteogenic differentiation. This work will inspire the integration of curved surfaces into cell platforms and scaffolds and provide a shape-memory strategy for curvature adjustment. STATEMENT OF SIGNIFICANCE: This work aims at the overlooked role of substrate curvature in regulating bone marrow stromal cells (BMSCs) fate by engineering shape-memory polymer (SMP) microspheres as an emerging platform for providing tunable curvatures, overcoming the limitation that existing platforms usually offer non-adjustable curvatures, hindering systematic analysis of the effects of curvature on BMSCs fate. SMP microspheres are programmed into ellipsoidal shapes with varying curvatures, and it is found that larger curvature induces greater BMSCs nuclear deformation. Crucially, curved surfaces significantly enhance BMSCs osteogenic differentiation compared to flat surfaces, with a curvature-dependent manner; larger curvature shows stronger promotion effect on osteogenic differentiation. This work develops a curvature-tunable cell substrate using SMP microspheres; it will inspire the integration of curvature cues into tissue scaffolds and curvature adjustment by shape-memory technology.