Chemical substrate-enabled piezoelectric metabolic reprogramming therapy unlocks the vicious triad of diabetic wounds

作者：Min Ge, Zhaojiang Guo, Zesong Ruan, Yihong Ma, Zhiming Zhang, Haoru Dong, Tingwang Shi, Tingting Hu, Lanlu Lu, Yunfeng Chen, Han Lin, Chaoliang Tan · 发表于：Cell Biomaterials · 年份：2025 · DOI：10.1016/j.celbio.2025.100276 · 被引用次数：9 · 研究领域：Planarian Biology and Electrostimulation、Wound Healing and Treatments、3D Printing in Biomedical Research

The complex pathological environment of infection, inflammation, and immune dysfunction in diabetic wounds often contributes to chronic non-healing wounds. Here, we present an emerging piezoelectric metabolic reprogramming therapy dual-enabled by chemical catalysis and macrophage efferocytosis, aimed at disrupting this pathological triad through calcium-peroxidized barium titanate. The chemical substrate-enabling strategy decreases the energy barriers through catalytic substrate modulation, enabling efficient bacterial clearance via reactive oxygen species radicals. Furthermore, this strategy reprogrammed macrophage metabolism via a low-intensity ultrasound-triggered piezoelectric-calcium-mediated signaling pathway, restoring impaired efferocytosis and expanding the macrophage pool through efferocytosis-induced macrophage proliferation. In diabetic mouse models, such a strategy cleared persistent biofilm infections, promoted macrophage polarization toward the M2 phenotype, and facilitated the distribution of Th2 cells and regulatory T cells that promote healing, ultimately accelerating wound closure. These findings establish a paradigm-shifting approach that integrates piezocatalysis with immune-metabolic remodeling, providing a transformative strategy for diabetic wound management.