Temporal and spatial-adapted metal ions delivery system for spinal cord injury repair with Mg-Zn-doped bilayer bioactive glasses

In clinical practice, ion supplementation therapy has demonstrated excellent clinical efficacy in spinal cord injury (SCI) repair. However, due to the spatiotemporal dynamics of ion imbalance following SCI, targeted phase-adapted ion supplementation strategies for SCI repair remain challenging. To address this issue, a spatiotemporally adapted metal-ion delivery system, Mg-Zn-doped bilayer bioactive glasses (Mg-Zn/BGs), was developed. It had a diameter of approximately 125 nm and comprised an Mg/BGs outer shell and a Zn/BGs inner core. The core-shell structure of Mg-Zn/BGs enables phase-specific sustained release of Mg²⁺/Zn²⁺ during SCI pathological progression. The early release of Mg²⁺ attenuated macrophage-induced inflammation by promoting macrophage polarization toward M2 type, which further inhibited scar formation, and thereby created a favorable microenvironment for subsequent neural regeneration. The release of Zn²⁺ at the late phase effectively promoted neural cell proliferation and regeneration, which was accompanied by axonal regeneration and re-myelination, leading to significant behavioral recovery of SCI mice. This study highlights the essential regulatory functions of metal ions across distinct stages of SCI recovery, demonstrating the development of a core-shell structured delivery platform capable of stage-optimized ion release. The engineered Mg-Zn/BGs effectively bridges the therapeutic gap between inflammation modulation and neuronal tissue regeneration, offering a potential solution for SCI treatment through its dual-phase ion coordination mechanism.