From Fibrous Building Blocks to Hierarchical Bone Scaffolds: A Biomimetic Strategy for Mechanical Optimization

The repair of large-segment bone defects remains a clinical challenge due to the lack of ideal scaffolds that simultaneously provide mechanical compatibility and effective biological guidance. Inspired by the hierarchical organization of native cancellous bone, in which trabeculae serve as building blocks that assemble into a transversely isotropic architecture, this study proposes a ″building blocks construction–biomimetic assembly″ strategy. Gelatin nanofibers were first fabricated via electrospinning and employed as building blocks to emulate bone trabeculae. Drawing on the natural Bouligand structures, a series of fibrous scaffolds, including random fiber bundles (RFB), unidirectional oriented fiber bundles (U-OFB), perpendicular oriented fiber bundles (P-OFB), single Bouligand-inspired oriented fiber bundles (SB-OFB), and double-twisted Bouligand-inspired oriented fiber bundles (DB-OFB), were successfully constructed through designed stacking and compression postprocessing routes. Multiscale mechanical evaluations demonstrated that the biomimetic DB-OFB exhibited the most favorable overall performance. Its macroscopic tensile strength and toughness were enhanced, resulting in mechanical behavior that closely approaches the transverse quasi-isotropic characteristics of cancellous bone. At the microscale, the nanoindentation modulus (5.37 ± 1.42 GPa) and hardness (0.25 ± 0.13 GPa) were higher than those of the other groups. Biological assessments further revealed that the fibrous scaffolds possessed good biocompatibility and that the aligned fiber topology effectively guided directional cell elongation. Thus, the DB-OFB architecture shows potential in mimicking the transversely isotropic behavior of cancellous bone while simultaneously achieving strength–toughness synergy and cellular guidance, thereby providing a biomimetic paradigm and an experimental foundation for the design of high-performance bone tissue engineering scaffolds.