Cascade Biomineralization of Geometrically Tuned Osteon-Mimetic Composite Biovesicle-Hydrogel Coating Improves Ti Implant-Assisted Repair of Osteoporotic Bone Fractures

Ti-based implants are a mainstream treatment modality for bone fracture treatment, but their osseointegration is severely hampered by osteoporosis-associated biomineralization disorder. This study reports a multifunctional hydrogel-biovesicle composite coating capable of enhancing interfacial biomineralization in a cascade manner to facilitate Ti-based implant osteointegration. For this purpose, we first prepared azido-tagged osteoblast membrane vesicles through glycoengineering of live osteoblasts for loading calcitriol (VD3), which were then facilely conjugated to hydrogels composed of phosphorylated gelatin (P-gel) and dibenzocyclooctyne-modified carboxymethyl chitosan through click reaction. Notably, liquid nitrogen-assisted directional freezing fabrication technology was applied during hydrogel preparation to mimic the extracellular matrix (ECM) pattern in healthy osteons for enhancing Ca²⁺ influx and osteogenic differentiation of adherent osteoblasts, while the biovesicle-mediated in situ VD3 delivery could further boost cellular Ca/P metabolism and mineral precursor excretion to accelerate ECM mineralization. These functions could act in a cooperative manner to promote new bone formation at the bone-implant interface to accelerate Ti-based implant osteointegration, presenting a promising approach for osteoporotic bone fracture repair in the clinic.