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Persistent high blood sugar induces mitochondrial oxidative stress and mtDNA leakage, activates the macrophage STING signaling pathway, leading to continuous secretion of pro-inflammatory factors, causing the wound healing process to stagnate in the inflammatory stage. This study developed a glucose/active oxygen dual-responsive hydrogel dressing. Borate ester dynamic cross-linking was used to combine chloroacetic acid with gelatin and modified alginate. At the same time, a STING inhibitor H151 lipidosome targeting macrophages was integrated into the hydrogel. This hydrogel has injectability, stretchability, and self-healing properties. After injection into diabetic wounds, it disintegrates due to the increase in high blood sugar and active oxygen, and releases CGA and HPSL as needed. CGA clears active oxygen and alleviates oxidative stress; HPSL specifically targets macrophages, inhibits the STING pathway, promotes anti-inflammatory phenotype polarization, reduces pro-inflammatory factors, and increases anti-inflammatory factor release. The hydrogel as a whole promotes angiogenesis and collagen deposition, accelerating wound healing. Innovation Points
① New target intervention: For the first time, the STING signaling pathway was used as a therapeutic target for diabetic wounds;
② Dual-response delivery: The glucose and reactive oxygen species dual-response hydrogel realizes on-demand disintegration and drug release;
③ Precise targeting of macrophages: Phosphatidylserine liposomes achieve specific delivery of STING inhibitors to macrophages.
Material development
1 Materials
The chlorogenic acid-bound gelatin was dynamically cross-linked with sodium alginate containing 3-amino-benzylamine, forming a glucose/reactive oxygen species dual-response hydrogel, and integrating STING inhibitor H151 liposomes with macrophage targeting.
2 Function
This hydrogel disintegrates on demand in high glucose and oxidative stress microenvironments, releasing chlorogenic acid to eliminate reactive oxygen species, and simultaneously delivers H151, which inhibits the STING pathway in macrophages through liposome targeting, thereby blocking the inflammatory cascade and promoting healing.
Thought extension
This work provides a new idea for the intervention of STING signaling axis-mediated immune disorders in chronic diabetic wounds. In the future, it can explore the optimization of different STING inhibitors, targeted delivery carriers, and the universality of mitochondrial damage-inflammation coupling mechanisms in other inflammatory-related disease models, further promoting the transformation of chronic wound treatment from "symptomatic anti-inflammation" to "precise regulation of the source signaling pathway".
Original source
Bioactive Materials (IF 20.3) Pub Date : 2026-03-17,
DOI: 10.1016/j.bioactmat.2026.03.025 Xingtong Wang, Yang Liu, Tianqi Nie, Zihan Tang, Jinjin Tao, Qiuyue Wang, Xutao Ma, Wanli Chu, Zerui Li, Changqing Zhu, Hao Guan, Shizhao Ji, Zhiyu He, Chuanan Shen
