Ion-Chelating Hydrogel Regulates Porous Zinc Scaffold Degradation for Osteoimmune Bone Repair.

Biodegradable metal scaffolds hold great promise for bone repair, yet their clinical translation is hindered by uncontrolled corrosion, rapid ion release, and adverse immune responses, particularly in porous architectures. Here, we report a hybrid scaffold that integrates a cancellous bone-mimicking porous zinc framework with an interpenetrating poly(vinyl alcohol)/TEMPO-oxidized cellulose nanofiber (PVA/TOCN) hydrogel. This design exploits hydroxyl- and carboxyl-mediated chelation of Zn2 + to regulate corrosion kinetics and stabilize ion release, while simultaneously reinforcing the hydrogel through secondary ionically crosslinked networks that provide extracellular matrix-like bioactivity. In vitro, the hybrid scaffold maintained >80% cell viability for 14 days, promoted osteogenic differentiation, and polarized macrophages toward a pro-regenerative phenotype. In a rabbit bone defect model, it accelerated bone regeneration, reduced inflammation, and improved scaffold-bone integration. By synchronizing degradation with tissue repair, this strategy establishes a class of immuno-instructive, biodegradable implants with potential for orthopedic translation.