Acoustically Assisted Heterojunction Hydrogel Promotes Angiogenesis and Tissue Regeneration by Modulating the Inflammatory Microenvironment

ABSTRACT

The healing of diabetic chronic wounds is hindered by multiple pathological barriers, including oxidative stress imbalance induced by hyperglycemia, persistent bacterial infection, and impaired neovascular function. This study developed an F127–HA–BiOCl@CeO ₂ (FHBC) hydrogel dressing with acoustic responsiveness, achieving tissue repair through systematic intervention in the unstable wound microenvironment. The system utilizes the acoustic streaming effect induced by low‐intensity ultrasound (US) to effectively overcome the barrier posed by viscous exudate in chronic wounds to the deep diffusion of active components. The core mechanism involves electron orbital hybridization between BiOCl and CeO ₂ , facilitating interfacial charge transfer. This enables the loaded CeO ₂ nanoenzymes to fully utilize their abundant oxygen vacancies and Ce ³⁺ /Ce ⁴⁺ redox pairs. This process achieves efficient capture and conversion of excess reactive oxygen species (ROS), significantly alleviating oxidative stress damage to endogenous cells. Concurrently, the system synergistically employs acoustic physical effects to suppress pathogen proliferation and disrupt biofilm physical structures. As the redox homeostasis of wound is restored, the dressing further mediates transformation of the local immune microenvironment. It induces pro‐inflammatory macrophages to polarize toward a reparative state, thereby releasing inhibition on the vascular endothelial growth signaling pathway. In vitro and in vivo experiments confirm that this system achieves deep integration of antibacterial, antioxidant, and immunomodulatory functions through the synergistic effects of acoustically assisted permeation and electronic energy level catalytic equilibrium. This promotes functional vascular network reconstruction and skin tissue regeneration in diabetic wounds.