The healing of diabetic foot ulcers is restricted by three interrelated obstacles: immune microenvironment imbalance, repeated infections, and insufficient angiogenesis. Existing dressings mostly address a single factor and lack systematic regulatory capabilities. This study proposes the "intelligent response - collaborative regulation" strategy, designing a manganese-doped zeolite imidazolate framework-8 containing desferrioxamine. This system possesses dual enzymatic activities, capable of eliminating excessive reactive oxygen species and resisting infection and promoting angiogenesis after decomposition. Further, a glucose and reactive oxygen species responsive chitosan-based hydrogel containing DFO@Mn-ZIF-8 and umbilical cord mesenchymal stem cell exosomes was constructed. In the infectious diabetic wound model, this hydrogel continuously senses and responds to the dynamic microenvironment, simultaneously achieving bacterial clearance, immune reconstruction, and angiogenesis, creating a pro-healing microenvironment.
Research Highlights
This study constructs an intelligent responsive hydrogel that integrates the enzymatic simulation activity of metal-organic frameworks and the regenerative function of stem cell exosomes on a glucose/reactive oxygen dual-responsive platform, achieving precise sensing and collaborative regulation of the complex pathological microenvironment of diabetic foot ulcers. This system eliminates reactive oxygen species, releases antibacterial and angiogenic components in response, and simultaneously reconstructs the immune microenvironment, providing an "sensing - responding - repair" integrated intelligent treatment paradigm for complex chronic wounds.
Innovations
① Intelligent response design: dual response mechanism to precisely sense the pathological microenvironment;
② Enzymatic simulation activity: Mn-ZIF-8 possesses dual enzymatic activities, actively eliminating reactive oxygen species;
③ Proposing a new "metal-immune" coupling treatment paradigm, expanding the limitations of traditional single-modal treatment.
Material Development
1 Materials
The Exo/MOF@CPH intelligent system was constructed by loading the manganese-doped zeolite imidazolate framework-8 and umbilical cord mesenchymal stem cell exosomes onto a glucose/reactive oxygen dual-responsive chitosan-based hydrogel.
2 Functions
This hydrogel senses changes in glucose and reactive oxygen levels in the microenvironment, responds by eliminating reactive oxygen species, resisting infection, promoting angiogenesis, and collaboratively rebuilding the immune microenvironment, achieving multi-targeted collaborative repair.
4 Extension of ideas
This work provides a new idea for multi-targeted collaborative treatment of intelligent responsive materials in complex chronic wounds. In the future, it can explore the regulation of enzymatic activity of different metal-organic frameworks, the optimization of response element combinations, and the universal application of multiple pathological signal collaborative sensing mechanisms in other difficult-to-heal tissue defect models, further promoting the transformation of wound dressings from "passive coverage" to "intelligent diagnosis and treatment". 
Original Source
Bioactive Materials (IF 20.3) Pub Date: 2026-03-20, DOI: 10.1016/j.bioactmat.2026.03.034 Haiyang Lin, Zengguang Wang, Ping Li, Yiwei Zhang, Weize Kong, Xiaokun Yue, Liang Feng, Zhouhao Chen, Yue Zheng, Zhiang Hu, Zilin Li, Hao Yang, Yihao Liu, Zeke Guo, Fang Cheng, Shuangqing Wang, Dezhi Lu, Jinwu Wang