3D printing combined with pH-induced 4D printed iron(III)-oxidized starch gels for controlled iron delivery and enhanced iron supplementation.

Abstract

To address iron deficiency anemia (IDA), a pH-triggered 4D-printed ferric oxidized starch gel system (4D-FeOMS) was constructed by integrating hot-extrusion 3D printing with stimulus-responsive structural transformation. Iron ions were coordinated within oxidized starch networks through ionic crosslinking. Rheological and spectroscopic characterization (FTIR, XPS) confirmed enhanced molecular entanglement and network uniformity in 4D-FeOMS relative to conventional 3D-printed counterparts. In vitro digestion assays demonstrated gastric retention of iron (release below 30%) followed by rapid liberation exceeding 85% in the proximal small intestine. In IDA mouse models, 4D-FeOMS restored hematological and biochemical indices, recovered organ iron stores by more than 94.6%, and elevated antioxidant enzyme activity, surpassing both iron salt controls and 3D-FeOMS. Mechanistic analysis indicated that hepcidin expression was modulated and ferritin/transferrin levels were regulated, collectively promoting systemic iron transport. The 4D-FeOMS formulation with 10% iron addition showed optimal complexation and supplementation performance.

Mechanism

4D-FeOMS modulates hepcidin expression and regulates ferritin/transferrin levels to facilitate systemic iron transport; it also enhances antioxidant enzyme activity, collectively improving iron bioavailability in IDA conditions.