Multifunctional nanocomposite with stage-responsive behavior for wound healing.

Chronic wounds, particularly refractory diabetic ulcers, typically fail to heal due to a self-perpetuating inflammatory state driven by persistent bacterial infection, severe oxidative stress, and impaired microvascular regeneration. Conventional static dressings cannot accommodate the spatiotemporal, multiphase complexity of tissue repair. Here, a stage-responsive hierarchical nanocomposite (SNF@GQDs@Arg) was engineered by covalently anchoring graphene quantum dots (GQDs) onto radially porous silica nanoflowers (SNF), followed by surface adsorption of L-arginine (L-Arg). The resulting platform coordinates wound repair through an integrated tripartite-physical, catalytic, and metabolic-cascade. In the initial hemostatic phase, the high-aspect-ratio topography of SNF enables rapid wound closure via a non-covalent nano-bridging effect. During the inflammatory phase, the immobilized GQDs act as peroxidase-mimicking nanozymes, converting pathological hydrogen peroxide (H2O2) into bactericidal hydroxyl radicals (·OH) to eradicate biofilms while simultaneously scavenging excess free radicals to resolve the reactive oxygen species (ROS) paradox. Concurrently, the sustained release of L-Arg replenishes the substrate pool for macrophage inducible nitric oxide synthase (iNOS), restoring physiological nitric oxide (NO) bioavailability. This metabolic intervention drives pro-inflammatory M1-to-reparative M2 phenotype transition, upregulates CD31 and VEGF expression to stimulate angiogenesis, and promotes organized collagen deposition. In a murine infected full-thickness skin defect model, SNF@GQDs@Arg markedly accelerated wound closure, suppressed local inflammation, and enhanced tissue remodeling quality without inducing systemic toxicity. By synchronizing functional bioactivity with the endogenous repair rhythm, this platform provides a microenvironment-adaptive paradigm for refractory chronic wound therapy.