Structural　engineering　is　an　appealing　means　to　modulate　osteogenesis　without　the　intervention　of　exogenous　cells　or　therapeutic　agents.　In　this　work,　a　novel　3D　scaffold　with　anisotropic　micropores　and　nanotopographical　patterns　is　developed.　Scaffolds　with　oriented　pores　are　fabricated　via　the　selective　extraction　of　water-soluble　polyethylene　oxide　from　its　poly(epsilon-caprolactone)　co-continuous　mixture　and　uniaxial　stretching.　The　plate　apatite-like　lamellae　are　subsequently　hatched　on　the　pore　walls　through　surface-induced　epitaxial　crystallization.　Such　a　unique　geometric　architecture　yields　a　synergistic　effect　on　the　osteogenic　capability.　The　prepared　scaffold　leads　to　a　19.2%　and　128.0%　increase　in　the　alkaline　phosphatase　activity　of　rat　bone　mesenchymal　stem　cells　compared　to　that　of　the　scaffolds　with　only　oriented　pores　and　only　nanotopographical　patterns,　respectively.　It　also　induces　the　greatest　upregulation　of　osteogenic-related　gene　expression　in　vitro.　The　cranial　defect　repair　results　demonstrate　that　the　prepared　scaffold　effectively　promotes　new　bone　regeneration,　as　indicated　by　a　350%　increase　in　collagen　I　expression　in　vivo　compared　to　the　isotropic　porous　scaffold　without　surface　nanotopology　after　implantation　for　14　weeks.　Overall,　this　work　provides　geometric　motifs　for　the　transduction　of　biophysical　cues　in　3D　porous　scaffolds,　which　is　a　promising　option　for　tissue　engineering　applications.　This　study　presents　a　3D　scaffold　featuring　anisotropic　micropores　and　nanotopographical　patterns　to　modulate　osteogenesis.　The　scaffold,　fabricated　through　selective　extraction,　uniaxial　stretching,　and　surface-induced　epitaxial　crystallization,　possesses　a　unique　geometric　architecture,　which　significantly　enhances　bone　mesenchymal　stem　cell　proliferation　and　osteogenic　differentiation,　leading　to　effective　cranial　defect　repair　and　promising　implications　for　tissue　engineering　applications.　image