Hierarchical Nanoplatform Integrating Oxidative-Acidic Microenvironment Remodeling and Bone Homeostasis Modulation for Diabetic Bone Defect Therapy.

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 Ca2 + release to support BMSC viability and osteogenic differentiation. The immobilized Ce-MOF component eliminates excessive ROS via reversible Ce3 +/Ce4 + 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.