Peptide coacervate-Prussian blue hybrid supraparticle-tailored scaffolds for revitalizing diabetic heart valve regeneration via multiplex oxidative stress regulation.

Diabetes mellitus impairs the regenerative capacity of valvular patients and poses a major barrier to successful reconstruction of autologous heart valves via in situ tissue-engineered heart valves (TEHVs). Herein, we developed a TEHV scaffold that integrates oxidative stress regulation with pro-endothelialization interfaces to reshape the hostile repair environment under diabetic conditions. A multifunctional supraparticle comprising a coacervate formed through electrostatic interaction between two highly charged oligopeptides, SS-31 and an REDV-derived peptide, anchored onto Prussian blue nanoparticles (PBNPs), was incorporated into a decellularized scaffold. This supraparticle-functionalized scaffold not only selectively enhanced endothelial cell (EC) adhesion via the REDV motif but also provided mitochondrial protection through SS-31, and facilitated reactive oxygen species elimination via the superoxide dismutase and catalase-mimicking activities of PBNPs. Through these synergistic mechanisms, the scaffold reduced EC apoptosis and promoted EC proliferation and migration under hyperglycemic conditions. Moreover, the scaffold alleviated hyperglycemia-induced oxidative stress in macrophages, thereby suppressing inflammatory cytokine expression. Implantation in diabetic rabbit vascular models demonstrated that this scaffold accelerated the formation of a functional endothelial layer and promoted favorable extracellular matrix remodeling. This pathological microenvironment-driven in situ TEHV scaffold design offers new insights into precision biomaterials development for patient-specific cardiovascular regenerative therapies.