Coordination-Stabilized Manganese(IV) Peptide Hydrogels Reveal Valence-Dependent Structure and Immunomodulation.

High-valence manganese is typically confined to solid oxide precursors in manganese-based biomaterials, leaving valence-dependent coordination-structure-function relationships largely unresolved. Here, we established a peptide-coordinated hydrogel platform that stabilized Mn(IV) in an aqueous/gel environment and enabled direct comparison between Mn(II)- and Mn(IV)-dominated supramolecular networks. By tuning FE tandem repeats, two representative systems, FE3-Mn(II) and FE4-Mn(IV), were constructed with distinct manganese valence distributions and coordination environments. These valence-defined hydrogels exhibited differentiated secondary-structure organization, nanofiber hierarchy, and viscoelastic relaxation behavior, indicating that manganese valence governed both network topology and dynamic reorganization. Functionally, FE3-Mn(II) more effectively enhanced innate immune priming, whereas FE4-Mn(IV) more strongly promoted redox stress and immunogenic cell death-associated signals. In a 4T1 tumor model, both hydrogels suppressed tumor growth and enhanced intratumoral immune infiltration, with FE4-Mn(IV) showing stronger overall antitumor efficacy and more spatially organized immune distributions. These results identified metal valence as a definable coordination variable in peptide hydrogels and revealed how valence-dependent network structure and dynamics relate to downstream immunomodulatory outputs, providing a basis for the design of manganese-based local immunomodulatory biomaterials.