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

en This link goes to a English section zh This link goes to a Chinese section 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. 摘要 en This link goes to a English section zh This link goes to a Chinese section 糖尿病慢性创面的愈合受到多重病理屏障的阻碍,包括高糖诱导的氧化应激失衡、持续性细菌感染以及新生血管功能受损等。为此,本研究构建了一种具有超声响应特性的F127–HA–BiOCl@CeO 2 (FHBC)水凝胶敷料,通过对不稳定创面微环境进行系统性干预,实现组织修复。该体系利用低强度超声(US)诱导的声流效应,有效克服慢性创面黏稠渗出液对活性组分向深层组织扩散的阻碍。其核心机制在于BiOCl与CeO 2 之间的电子轨道杂化促进界面电荷转移,使负载的CeO 2 纳米酶能够充分发挥丰富氧空位以及Ce 3+ /Ce 4+ 氧化还原对的作用,从而高效捕获并转化过量活性氧(ROS),显著缓解内源性细胞所受的氧化应激损伤。同时,该系统协同利用超声的物理效应抑制病原菌增殖并破坏生物被膜结构。随着创面氧化还原稳态的恢复,敷料进一步调控局部免疫微环境,诱导促炎型巨噬细胞向修复型表型极化,从而解除对血管内皮生长信号通路的抑制。体内外实验结果表明,该体系通过声辅助渗透与电子能级催化平衡的协同作用,实现了抗菌、抗氧化及免疫调节功能的深度整合,促进了糖尿病创面功能性血管网络的重建及皮肤组织再生。