Multifunctional nanocomposite with stage-responsive behavior for wound healing.

Abstract

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.