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Thermoplastic semi-crystalline polymers are excellent candidates for tissue engineering scaffolds thanks to facile processing and tunable properties, employed in melt-based additive manufacturing. Control of crystallization and ultimate crystallinity during processing affect properties like surface stiffness and roughness. These in turn influence cell attachment, proliferation and differentiation. Surface stiffness and roughness are intertwined via crystallinity, but never studied independently. The targeted stiffness range is besides difficult to realize for a single thermoplastic. Via correlation of thermal history, crystallization and ultimate crystallinity of vitamin E plasticized poly(lactide), surface stiffness and roughness are decoupled, disclosing a range of surface mechanics of biological interest. In osteogenic environment, human mesenchymal stromal cells were more responsive to surface roughness than to surface stiffness. Cells were particularly influenced by overall crystal size distribution, not by average roughness. Absence of mold-imposed boundary constrains makes additive manufacturing ideal to spatially control crystallization and henceforward surface roughness of semi-crystalline thermoplastics. Graphic abstract