Mantis shrimp saddle-mimetic amorphous calcium (zinc) phosphate/chitin scaffolds with superior mechanical properties...

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. In vitro 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.