Magnetically bioprinted anisotropic hydrogels promote BMSC osteogenic differentiation for bone defect repair

Bone tissue engineering utilizing magnetic anisotropic hydrogels (MAHs) loaded with bone marrow-derived stem cells (BMSCs) offers a promising strategy to enhance the regeneration of bone defects due to their mechanotransduction and osteoinductive properties. However, the application of MAHs as bioinks for creating personalized 3D scaffolds faces significant challenges. Bioprinting necessitates a rapid sol-gel transition to enable the ink to form stable structures, whereas anisotropic shaping requires the ink to remain in a sol state post-printing, allowing magnetic particles to assemble freely under magnetic induction. To overcome these challenges, we develop a biomimetic MAH that recapitulate the anisotropic structures of the bone using a continuous Liquid-in-Liquid bioprinting method combined with magnetic induction. The constructed MAHs feature uniformly aligned Fe₃O₄ microfibers embedded within the bioprinted hydrogel filaments. These Fe₃O₄ microfibers provide microscale geometric cues that promote the elongation and osteogenic bioactivity of BMSCs through biomechanical signaling pathways. The implantation of the MAHs loaded with BMSCs in a critical-sized cranial defect model effectively accelerates the healing of bone injuries by facilitating collagen matrix development and promoting neovascularization. This study introduces a novel approach in the development of MAHs and presents a promising candidate for applications in bone tissue engineering and repair.