Since mechanotransduction and interactions at the interface between materials and cells play crucial roles in the regulation of cell behaviors and the genotype-to-phenotype relation ship, mechanical properties are important parameters in the Cells sense and respond to a wide range of external signals, including chemical signals, topography, and interface mechanics, via interactions with the extracellular matrix (ECM), triggering the regulation of behavior and function. The ECM can be considered a hierarchical multiphase porous matrix with various components. Highly porous hydrogel-based biomaterials can mimic the critical ECM properties, to provide mechanical support for tissues and to regulate cellular behaviors, such as adhesion, proliferation, and differentiation. Herein, based on micro/nanoscale-topography-coupled mechanical action, recent advances in the fabrication and application of hydrogel composites with tunable mechanical properties and topography in biomedicine are summarized. In particular, recent findings showing that hydrogels with specifically designed structures not only influence a range of cellular processes and fit the needs of engineered tissues but also have pharmacological effects are emphasized. Hydrogels
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