Mechanical Stimulus and Metabolic Responses by Cryo‐Printing Anisotropic Scaffolds for Achieving Promoted Bone Regeneration

Abstract 3D scaffolds are essential as they serve as extracellular matrix (ECM)‐like platforms to provide cells with mechanical support and facilitate their attachment for bone regeneration. As an emerging personalized treatment technology, 3D printing has been applied to treat irregular large‐area bone defects caused by diseases such as tumors and trauma. However, traditional printing methods cannot control the microstructure of the scaffolds for bone tissue engineering (BTE). Meanwhile, commercial materials often cause rejection reactions, limiting the osteogenic effect of 3D‐printed scaffolds. In this investigation, scaffolds with controllable micro‐ordered morphology are prepared through cryogenic 3D printing combined with ice template technology. The surface of the scaffold exhibits an ordered micrometer‐level structure that matches the growth direction of ice crystals, and the porosity of the scaffolds can be adjusted by the content of nano‐hydroxyapatite (HA). The biological studies reveal an increased osteogenesis and angiogenesis of the composite scaffolds. The anisotropic mechanical stimulation signal regulates metabolic patterns, which may be a potential mechanism for anisotropic scaffolds to promote osteogenic differentiation by regulating S1P/S1PR2/YAP metabolic pathway. This study unlocks the potential of this simple method to produce biomimetic anisotropic scaffolds to achieve multiple functions for BTE.