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Upon contraction, the silk fibroin (SF)-shape-memory polymer (SMP) bilayer produces wrinkles. Results support the potential use of biopolymer wrinkles on active materials in biomedical applications, such as cell mechanobiology or tissue engineering. 

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 Peripheral nerve injuries (PNIs) resulting in myelin breakdown and axonal degeneration at both the proximal and distal nerve stumps are major clinical concerns that can induce functional loss and diminished quality of life. In biomaterials science, considerable attention has been given to artificial nerve guidance conduits (NGCs), since the engineered tubular structures have the potential to supply a supportive nerve microenvironment to longitudinally align the regenerating axons for bridging the injured nerve sites. Although NGCs may become promising alternatives to nerve autografts, the fabrication approaches available to incorporate directional cues for dictating neuronal behavior and nerve reconnection have been limited to conventional micro/nano‐fabrication techniques that are complex and time‐consuming due to manual processing steps. Thus, our goal here was to develop a simple manufacturing approach for introducing topographical cues onto NGCs. To achieve this goal, we used an established mechanically actuated silk wrinkling approach to create topographically functionalized surfaces as a potential NGC material platform for guided directional alignment of neurons. We 3D‐printed thermo‐responsive shape‐memory polymer (SMP)‐based NGCs that can produce silk fibroin (SF)‐wrinkled topographies on the micro and nano‐meter length scale. Since SF is a commonly used biomaterial surface coating with excellent neuro‐compatibility, we studied the ability to develop NGCs that can autonomously actuate silk wrinkles upon heat‐induced contraction of the SMP and evaluated the effects of the topographically functionalized construct on neuronal behavior. Using an immortalized dorsal root ganglion neuronal cell line, we found that the silk‐wrinkled conduits displayed high neuronal viability and adhesion compared to uncoated conduits and tissue‐culture polystyrene controls. We also found that the wrinkled conduits enabled the neurons to elongate and align parallel to the direction of the wrinkled topography. Longer neurite extension was also observed on the wrinkled conduits compared to their respective controls. These findings demonstrate the potential for functional wrinkled protein coatings to provide directional cues in the fabrication of artificial NGCs for peripheral nerve repair. 

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.