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While current scaffolds have the potential to promote the repair of critical-sized defects, this capacity is hindered by their inadequate bioactivity and osteoconductivity. Therefore, a nano-\/micro-hierarchical scaffold with a tunable surface architecture was developed to enhance bone regeneration. The resulting biointerface markedly promoted osteogenic differentiation of bone marrow mesenchymal stem cells in a non-linear, roughness-dependent manner. Furthermore, in vivo results displayed that scaffolds with a fiber roughness of approximately 400\u2009nm exhibited the highest potency on bone defect repair. The promising performance of the hierarchical scaffold was found to result from enhanced cellular mechanotransduction by its nano-\/micro-hierarchical architectures at the scaffold\u2019s biointerface. The present study offers an interesting strategy to address the challenge of critical-sized bone defect repair based on mechanobiology.<\/jats:p>","DOI":"10.1093\/rb\/rbag136","type":"journal-article","created":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T12:28:57Z","timestamp":1781612937000},"source":"Crossref","is-referenced-by-count":1,"title":["Engineered hierarchical 3D scaffold promotes bone regeneration through enhanced mechanotransduction"],"prefix":"10.1093","volume":"13","author":[{"given":"Dan","family":"Wu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University , Chengdu, Sichuan 610041,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Dai","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases & National Center for 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