Hierarchical Nanoplatform Integrating Oxidative-Acidic Microenvironment Remodeling and Bone Homeostasis Modulation...

Diabetic craniofacial bone defects exhibit unsatisfactory repair attributed to synergistic oxidative stress, local acidification and disordered bone immunity, whereas conventional mono-functional biomaterials are incapable of synchronously resolving these interlocked pathological cascades. Herein, a hierarchical nanoplatform (CM/LDH) is fabricated by immobilizing Ce-MOF nanozyme onto CaAl-LDH substrate for synergistic bone remediation. As an alkaline and bioactive support, CaAl-LDH improves peri-defect microenvironment acidification to preserve the redox catalytic activity of loaded Ce-MOF, accompanied with sustained Ca^{2 +} release to support BMSC viability and osteogenic differentiation. The immobilized Ce-MOF component eliminates excessive ROS via reversible Ce^{3 +}/Ce^{4 +} cycling, further alleviating inflammatory polarization of macrophages and cutting off pathological cell crosstalk. Benefiting from mutual complementary functions, CM/LDH synchronously rectifies oxidative-acidic microenvironment and rebalances osteogenic-osteoclastic turnover, overcoming inherent drawbacks of single-target interventions. This synergistic nanosystem provides a potential biomaterial option for diabetic craniofacial bone regeneration.