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In Vivo Imaging of Reactive Oxygen Species in a Murine Wound Model
Published on: November 17, 2018
Reactive Oxygen Species Scavenging and Thermosensitive Smart Release-Stiffening Integrated Hydrogel for Diabetic
Haoning Qi1,2, Junyu Shi1, Xindi Wei1
1Department of Oral and Maxillofacial Implantology, Shanghai PerioImplant Innovation Center, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai 200011, China.
Abstract:
Diabetic wounds remain a formidable clinical challenge due to excessive reactive oxygen species (ROS) accumulation, impaired immune regulation, and compromised tissue regeneration. Herein, we report a multifunctional thermosensitive smart hydrogel integrating hollow mesoporous MnO2 nanozymes and transforming growth factor-β1 (TGF-β1) into an adhesive thermosensitive hydrogel (TGF-β1@MATH) for synergistic diabetic wound therapy. The MnO2 nanozymes efficiently scavenge ROS in the diabetic wound microenvironment, suppressing the Nrf2-HO-1-NQO-1 pathway to alleviate oxidative stress and restore the cell migration capacity. Triggered by body temperature, TGF-β1@MATH undergoes stiffness enhancement and controlled TGF-β1 release: the increased stiffness upregulates integrin β2 (ITGB2) expression in T cells, while TGF-β1 synergizes with ITGB2 to activate the Smad2/3 pathway, promoting regulatory T cell (Tregs) aggregation and secretion of growth factors. In vitro studies confirm that TGF-β1@MATH accelerates fibroblast migration, induces myofibroblast differentiation, and modulates the immune microenvironment. In diabetic mice, TGF-β1@MATH achieves a 95% wound healing rate within 14 days, significantly enhancing re-epithelialization, collagen deposition, angiogenesis, and Tregs recruitment. This integrated design addresses multiple pathological barriers of diabetic wound areas (WA) through ROS scavenging, thermosensitive regulation and immune-modulated regeneration, offering a promising translational strategy for clinical diabetic wound management.
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