Spatiotemporally Regulated Pro-/Anti-Inflammatory Transition via Reactive Oxygen Species-Sensitive Core–Shell Hydrogel for Diabetic Infected Wound Healing

Abstract

Diabetic infected wounds remain difficult to heal because bacterial colonization, biofilm formation, excessive reactive oxygen species (ROS), and persistent inflammation mutually reinforce one another in the diabetic wound microenvironment. In diabetic wounds, the temporal immune switch is often impaired, resulting in oxidative stress accumulation and poor vascularized tissue repair. Therefore, an ideal wound dressing should not merely kill bacteria or suppress inflammation independently, but should coordinate antibacterial intervention and immune remodeling according to the evolving stages of wound healing. Here, we constructed a ROS-responsive core–shell hydrogel, BBT-Py+ NPs@SchB@CSH, to achieve spatiotemporally ordered therapy for diabetic infected wounds. The outer shell was loaded with BBT-Py+ nanoparticles, an aggregation-induced emission luminogen (AIEgen) with near-infrared imaging capability and synergistic photothermal–photodynamic antibacterial activity against Staphylococcus aureus and biofilms. The inner core encapsulated schisandrin B (Sch B), a natural antioxidant and immunomodulator that scavenges excessive ROS and promotes macrophage polarization from the pro-inflammatory M1 phenotype toward the reparative M2 phenotype. The ROS-sensitive interface enabled the infected microenvironment and laser-triggered ROS to accelerate outer-shell degradation, allowing early antibacterial action to be followed by Sch B-mediated immunoregulatory repair. In vitro and in vivo evaluations demonstrated that BBT-Py+ NPs@SchB@CSH effectively disrupted bacterial biofilms, reduced bacterial burden, alleviated oxidative inflammatory stress, promoted collagen deposition and angiogenesis, and accelerated diabetic infected wound closure. This study presents an “outer-layer antibacterial, inner-core immunomodulatory repair” strategy that matches therapeutic function to the temporal requirements of infected diabetic wound healing.