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Despite notable progress in mimicking anisotropy, developing biomaterials that simultaneously exhibit high strength, and excellent biocompatibility remains a significant challenge. In this study, a novel strategy is proposed to fabricate multiscale, tendon\u2010mimetic regenerated silk fibroin (RSF) scaffold with a preferentially aligned microstructure and superior mechanical properties. This strategy integrates ethanol\u2010annealing to induce \u03b2\u2010sheet crystallization (nanoscale), freeze\u2010casting to create aligned microstructures (microscale), and densification to enhance interfacial bonding (macroscale). The synergistic effect of these multiscale structures effectively resists crack propagation, yielding impressive mechanical properties: a tensile strength of 7.8\u00a0MPa, elongation at break of 206%, and toughness of 14.52\u00a0MJ\u00a0m\n                    <jats:sup>\u22123<\/jats:sup>\n                    . Notably, the scaffold is fabricated through a purely physical process, free of chemical modifications or additives, preserving its biocompatibility and suggesting promising clinical potential. This biomimetic RSF scaffold promotes tendon cell adhesion, directional migration, and upregulated expression of tendon\u2010specific proteins. After 8 weeks of implantation in a rabbit full\u2010thickness Achilles tendon defect model, the scaffold effectively promoted realignment of the newly formed collagen fibers, resulting in a regenerated tendon structure that closely resembles native tendon architecture. This study provides insights into the design and manufacturing of high\u2010performance biomaterials.\n                  <\/jats:p>","DOI":"10.1002\/adhm.202500428","type":"journal-article","created":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T07:54:23Z","timestamp":1745481263000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Strong and Tough Tendon\u2010Mimetic Silk Fibroin for Tissue Regeneration"],"prefix":"10.1002","volume":"14","author":[{"given":"Guofeng","family":"Liu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Fluid Power and Mechatronic Systems &amp; Liangzhu Laboratory School of Mechanical Engineering Zhejiang University  Hangzhou 310027 China"},{"name":"The Second Affiliated Hospital of Zhejiang University Zhejiang University  Hangzhou 310027 China"},{"name":"Key Laboratory of 3D Printing Process and Equipment of Zhejiang Province College of Mechanical Engineering Zhejiang University  Hangzhou 310027 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengcheng","family":"Xia","sequence":"additional","affiliation":[{"name":"Sports Medicine and Joint Surgery Nanjing First Hospital Nanjing Medical University  Nanjing 210006 P. 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