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Surface wrinkling provides an approach to fabricate micron and sub-micron-level biomaterial topographies that can mimic features of the dynamic, in vivo cell environment and guide cell adhesion, alignment, and differentiation. Most wrinkling research to date has used planar, two-dimensional (2D) substrates, and wrinkling work on three-dimensional (3D) structures has been limited. To enable wrinkle formation on architecturally complex, biomimetic 3D structures, here, we report a simple, low-cost experimental wrinkling approach that combines natural silk fibroin films with a recently developed advanced manufacturing technique for programming strain in complex 3D shape–memory polymer (SMP) scaffolds. By systematically investigating the influence of SMP programmed strain magnitude, silk film thickness, and aqueous media on wrinkle morphology and stability, we reveal how to generate and tune silk wrinkles on the micron and sub-micron scale. We find that increasing SMP programmed strain magnitude increases wavelength and decreases amplitudes of silk wrinkled topographies, while increasing silk film thickness increases wavelength and amplitude. Silk wrinkles persist after 24 h in cell culture medium. Wrinkled topographies demonstrate high cell viability and attachment. These findings suggest the potential for fabricating biomimetic cellular microenvironments that can advance understanding and control of cell–material interactions in engineering tissue constructs. 

Abstract Bacterial biofilms on the surfaces of indwelling biomedical devices can cause long‐term infection and patient morbidity and mortality. Wrinkled surface topographies have previously demonstrated promising antifouling properties. Here we report a bioinspired strategy in which the actuation of silk fibroin produces tunable, wrinkled surface topographies on 2D shape memory polymer (SMP) substrates and investigate the influence of these topographies on biofilm formation. To mimic biofilm‐associated infections related to the geometries of indwelling medical devices, silk wrinkles are produced on complex, 3D SMP architectures, and biofilm formation is evaluated. Using common biofilm‐causing agents, smaller silk wrinkle wavelengths and amplitudes are found to significantly reduce biofilm formation, resulting in primarily isolated, single‐cell bacteria on the 2D wrinkled surfaces. These single‐cell bacteria are nearly completely eradicated by treatment with antibiotics, which are ineffective against control surfaces. Antibiotics are also physically incorporated into the 2D wrinkled surfaces, which resulted in a further significant reduction in bacterial adhesion. Lastly, silk wrinkled topographies are successfully applied on 3D architectures, and the wrinkled surfaces display a significant reduction in biofilm coverage compared to controls. The findings demonstrate the potential for biopolymer wrinkles on biomaterials to be used as antifouling surfaces for biofilm prevention.