Biomimetic Strategies for Bone Regeneration: Smart Scaffolds and Multiscale Cues

Bone regeneration remains difficult due to the complex bone microenvironment and the limited healing capacity of large defects. Biomimetic strategies offer promising solutions by using advanced 3D scaffolds guided by natural tissue cues. Recent advances in additive manufacturing, nanotechnology, and tissue engineering now allow the fabrication of hierarchical scaffolds that closely mimic native bone. Smart scaffold systems combine materials with biochemical and mechanical signals. These features improve vascularization, enhance tissue integration, and support better regenerative outcomes. Bio-inspired materials also help connect inert implants with living tissues by promoting vascular network formation and improving cell communication. Multiscale design approaches recreate bone nano- to macro-level structure and support both osteogenic activity and immune regulation. Intelligent and adaptive scaffolds are being developed to respond to physiological changes and enable personalized bone repair. This review discusses the current landscape of biomimetic scaffold design, fabrication techniques, material strategies, biological mechanisms, and translational considerations shaping next-generation bone regeneration technologies. Future directions focus on sustainable, clinically translatable biomimetic systems that can integrate with digital health tools for improved treatment planning.