Natural Silk Spinning‐Inspired Meso‐Assembly‐Processing Engineering Strategy for Fabricating Soft Tissue‐Mimicking Biomaterials

Abstract Natural silk spinning is the strategy used by spiders and silkworms to construct their ultra‐strong‐and‐tough silks. It can be considered as an optimized meso‐assembly processing engineering (MAPE) strategy that effectively coordinates molecular‐and‐supramolecular assembly and native spinning. Inspired by this process, this study develops a biomimetic MAPE strategy to fabricate biomaterials mimicking the structural and mechanical characteristics of biological tissues. The structural and mechanical mimetics are realized by synergistically integrating phase transition‐induced meso‐assembly and mechanical training‐induced structural remodeling. Through this approach, highly‐hydrated silk fibroin materials with exceptional tunable mechanical properties, such as softness, high stretchability (failure strain larger than 1200%), and high strength and toughness (strength of 5 ± 1 MPa, stiffness 18 ± 2 MPa, and toughness of 6 ± 1 MJ m −3 ) are produced. Thanks to their structural and mechanical tissue‐matching features, these biomimetic meso‐assembled materials exhibit advances in the modulation of different cell morphologies. The gradient architecture deformation (aspect ratio, spreading area, and perimeter) is evidenced, and the interplay between cytoskeleton (actin and tubulin) and matrix adaptation orientation is substantiated. These findings advance the application of silk fibroin biomaterials in the regulation of adaptive cell reconstruction, since the morphology of cells is the basis for their physiological functions.