Mantis shrimp saddle-mimetic amorphous calcium (zinc) phosphate/chitin scaffolds with superior mechanical properties and bioactivity for bone regeneration

Current bone scaffolds face the challenge of simultaneously providing sufficient mechanical support and optimal bioactivity, limiting their applications for the repair of large-sized bone defects. Inspired by the mantis shrimp saddle-like structure, we developed a triply saddle-mimetic Zn²⁺ doped amorphous calcium phosphate (ACZP)/chitin (ACZP/CT) scaffold that integrated structural, compositional, and functional biomimicry for bone regeneration. The ACZP/CT samples retained the amorphous state of nanoclusters, while the hierarchical assembly resulted in a flexural strength of approximately 160.09 MPa and significantly improved fracture toughness (up to 10.08 MPa m^1/2) through complex crack propagation along the gradient layers. <i>In vitro</i> studies indicated that the scaffold with ACZP nanoclusters effectively promoted osteogenesis and angiogenesis by releasing of Ca²⁺ and Zn²⁺ ions. The hierarchical gradient structure further induced early ingrowth of new vessels, thereby supporting extensive vascularized bone formation and achieving superior repair of cranial defects, with a bone volume/total volume of 68.39% after implantation for six months. Furthermore, RNA sequencing analysis showed that the bone regeneration mechanism was attributed to ACZP/CT-mediated synergistic activation of PI3K-Akt, MAPK and HIF-1 signaling pathways. These findings illustrate that the saddle-mimetic ACZP/CT scaffold collaboratively satisfies the dual requirements of mechanical adaptability and bioactivity for bone regeneration, offering a clinically translatable strategy for large-sized bone defect repair.