unfolding, [2] and skin wrinkles communicate a change in the state of the body. [3] These exquisite self-wrinkling processes typically originate from heterogeneous growth rates during the growth process, which results in compressive strains on the constrained tissues or organs and leads to mechanical instability. [5,6] Hydrogels possess water-rich structures similar to the abovementioned biological tissues and are regarded as promising scaffolds in biomedical fields. [7][8][9] Given the importance of wrinkled structures, the similarity between hydrogels and biotissue, and the important role of the programmable structure of hydrogels in potential biomedical applications, [10,11] imitating the delicate architecture of biological tissues in a biocompatible, mechanically stable wrinkled hydrogel with programmable patterns can facilitate an understanding of the effects of surface topography on biological properties and will be of benefit to humanity. In fact, motivated by the distinct functionalities of wrinkled structures in biology, material scientists have attempted to mimic this structure in artificial systems. [12][13][14][15][16][17][18][19] Consequently, a series of strategies, including swelling mismatch, [20] prepatterning treatment, [21] or coating of a second layer on the substrate, [5] have been successfully conducted to generate a compressive strain that triggers a controllable wrinkling Wrinkled hydrogels from biomass sources are potential structural biomaterials. However, for biorelated applications, engineering scalable, structure-customized, robust, and biocompatible wrinkled hydrogels with highly oriented nanostructures and controllable intervals is still a challenge. A scalable biomass material, namely cellulose, is reported for customizing anisotropic, all-cellulose, wrinkle-patterned hydrogels (AWHs) through an ultrafast, auxiliary force, acid-induced gradient dual-crosslinking strategy. Direct immersion of a prestretched cellulose alkaline gel in acid and relaxation within seconds allow quick buildup of a consecutive through-thickness modulus gradient with acid-penetration-directed dual-crosslinking, confirmed by visual 3D Raman microscopy imaging, which drives the formation of selfwrinkling structures. Moreover, guided by quantitative mechanics simulations, the structure of AWHs is found to exhibit programmable intervals and aligned nanostructures that differ between ridge and valley regions and can be controlled by tuning the prestretching strain and acid treatment time, and these AWHs successfully induce cell alignment. Thus, a new avenue is opened to fabricate polysaccharide-derived, programmable, anisotropic, wrinkled hydrogels for use as biomedical materials via a bottom-up method.The ORCID identification number(s) for the author(s) of this article can be found under https://doi.
