Large bone defects require scaffolds that combine mechanical support, biological activity, and anatomical adaptability.Metamaterials use deliberately designed structure to control effective properties beyond bulk composition.This narrative review examines metallic, ceramic, bioglass, polymeric, and composite metamaterial platforms for bone repair.It then considers mechanical, electroactive, magnetic, ultrasoundresponsive, photoresponsive, thermoresponsive, and shape-memory strategies.These structures can regulate modulus, stress transfer, pore connectivity, mass transport, degradation, and local stimulus delivery.The resulting local conditions influence bone ingrowth, vascularization, osteoimmune transitions, infection control, post-tumor reconstruction, and osseointegration.At the cell-material interface, structural and physical influence engage YAP/TAZ, integrin/FAK, Wnt/β-catenin, HIF-1α/VEGF, BMP/Smad, PI3K/Akt/mTOR, and MAPK signaling.Translation remains constrained by limited fatigue data, poorly resolved in vivo pathway crosstalk, manufacturing variability, and excessive system complexity.Future designs should match a defined clinical indication and prioritize scalable fabrication, predictable mechanical and degradation behavior, long-term remodeling, and clinically relevant validation.
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Liang et al. (2026) studied this question.
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