Oriented Nano-Homogeneous Biomimetic Scaffolds Regulate Cell Alignment and Promote Endogenous Bone Regeneration

Bone tissue engineering still faces challenges in achieving sufficient osteoinductivity and osteoconductivity, particularly when relying on conventional organic-inorganic composites with poorly defined structures. Here, inspired by the anisotropic architecture of native bone, a nano-homogeneous, radially oriented hybrid scaffold was constructed through directional freeze-casting technology for endogenous bone regeneration. Tunicate nanocellulose (TCNC) was employed as an efficient dispersant and mechanical reinforcer to achieve homogeneous dispersion of carbon nanotubes (CNT) within a chitosan (CS) matrix. Subsequent in situ biomimetic mineralization generated uniformly distributed hydroxyapatite (HAP), providing improved bioactivity. The incorporation of CNT endowed the scaffolds with strong photothermal antibacterial capability, achieving an antibacterial rate above 98% against S. aureus. Benefiting from the anisotropic channels, the oriented scaffolds promoted cell adhesion, alignment, and proliferation more effectively than random porous structures. In a rat cranial defect model, the oriented scaffold exhibited superior osteogenic performance, with bone mineral density reaching 0.688 g/cm³ after 3 months of implantation. Overall, this work demonstrates a structurally and functionally integrated biomimetic strategy for enhancing endogenous bone regeneration and underscores the importance of nano-homogeneous, anisotropic architectures in guiding tissue repair.