Smart gel tectonics: 3D-printed starch-chitosan architectures with pH-responsive magnesium delivery for targeted...

The development of effective oral magnesium supplements is hindered by two major delivery challenges: rapid gastric leakage leading to gastrointestinal side effects, and non-targeted intestinal release resulting in poor absorption and compensatory excretion. To address this, we engineered an intelligent, intestinal-targeted delivery system based on pH-responsive oxidized maize starch (OMS)-chitosan (CS) composite hydrogels, fabricated via hot-extrusion microwave 3D printing (HEM-3DP). The system exhibited a unique gastric-phase structural adaptation: acidic conditions trigger CS dissolution and OMS carboxyl protonation, initiating a dynamic "ionic handoff" where Mg²⁺ was recaptured by exposed CS amines via coordination bonds. This mechanism reduced gastric Mg²⁺ release by >40% compared to CS-free controls, enabling precise spatiotemporal control with sustained small intestinal release (66.6-74.0%) and enhanced colon-targeted delivery (33.6-56.0% retention). Release kinetics were finely tuned by engineering OMS carboxyl content (0.36-1.57%) and molecular weight (6.84 × 10⁵-2.39 × 10⁶ Da), demonstrating programmable design. In magnesium-deficient mice, the optimized OMS2-CS-Mg²⁺ gel not only restored serum magnesium to physiological levels (1.35 ± 0.04 mmol/L) but also upregulated key intestinal (claudin1) and colonic (TRPM6/7) absorption transporters-a dual-pathway activation unattained by conventional MgCl₂ supplementation. This work elucidated a clear structure-mechanism-performance relationship governing nutrient release and absorption. It provided a robust, food-grade platform that integrated advanced manufacturing with material intelligence to achieve site-specific, controlled mineral delivery, offering a translatable strategy for oral supplementation and broadening the design principles for smart, responsive hydrogel-based delivery systems.