Microstructured cellulose acetate biointerfaces regulate mesenchymal stem cell response and promote osteogenic commitment

Cellulose acetate (CA) is an attractive and sustainable biopolymer for biomedical applications due to its biocompatibility, tunable physicochemical properties, and compatibility with microfabrication. Mechanical stimuli such as topographical cues are known to profoundly influence stem cell behavior, yet their employment in cellulose acetate systems remains underexplored. In this study, we present a reproducible soft-lithography approach to engineer CA scaffolds with well-defined microstructured topographies and controlled surface roughness. The interfacial characteristics of the resulting biointerfaces were assessed using atomic force microscopy. Mesenchymal stem cells cultured on these microstructured platforms exhibited enhanced adhesion, cytoskeletal organization, and focal adhesion formation compared with flat CA controls. Notably, surfaces with intermediate roughness modulated the nuclear translocation of the mechanosensitive regulator TAZ, relative to flat and high roughness surfaces, in a topography dependent manner, suggesting activation of adhesive and cytoskeletal signaling pathways. Under osteogenic conditions, these biointerfaces further supported elevated alkaline phosphatase activity and osteopontin expression, indicative of enhanced early osteogenic commitment. Overall, this work demonstrates that microstructured CA biointerfaces act as instructive platforms that modulate mesenchymal stem cell response through topography-mediated mechanical cues, highlighting their potential as sustainable platforms for bone tissue engineering applications.