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A Protocol for Constructing a Rat Wound Model of Type 1 Diabetes
Published on: February 17, 2023
Pathology-driven catalytic nanozyme-integrated adhesive hydrogel disrupts the hyperglycemia-ROS-hypoxia loop to
Yu Cai1, Haifeng Liang1, Tianhua Xiao2
1Guangzhou Key Laboratory of Spine Disease Prevention and Treatment, Department of Orthopaedic Surgery, Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Medical Research Center for Obstetrics and Gynecology the Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, 510150, China.
Abstract:
Diabetes mellitus severely impair fracture healing due to a pathological microenvironment characterized by persistent hyperglycemia, excessive reactive oxygen species (ROS), tissue hypoxia, and chronic inflammation, which together suppress angiogenesis and osteogenesis. Most current biomaterial strategies target only a single pathological factor and therefore fail to disrupt the interconnected metabolic cascade that perpetuates tissue dysfunction. Here, we developed a pathology-driven catalytic nanozyme-integrated adhesive hydrogel (Gel-FQG) to simultaneously regulate hyperglycemia, oxidative stress, hypoxia, and immune imbalance in diabetic fractures. Gel-FQG incorporates glucose oxidase (GOx)-loaded Fe3+-quercetin nanozymes into a dynamic Schiff-base hydrogel network, providing strong tissue adhesion, injectability, and sustained catalytic activity. Through sequential glucose oxidation and H2O2 decomposition, Gel-FQG consumes excess glucose, scavenges ROS, and generates oxygen, thereby disrupting the hyperglycemia-ROS-hypoxia feedback loop. In vitro, Gel-FQG alleviates oxidative stress and hypoxia, promotes macrophage polarization toward the pro-regenerative M2 phenotype via suppression of the TNF-α/NF-κB/HIF-1α signaling, and enhances osteogenic and angiogenic responses under hyperglycemic conditions. In a diabetic rat femoral fracture model, local implantation of Gel-FQG significantly accelerates vascularized bone regeneration and fracture healing. These findings demonstrate that Gel-FQG actively remodels the diabetic fracture microenvironment and offers a promising strategy for diabetic bone repair.
Insights
This study presents a novel hydrogel that simultaneously addresses hyperglycemia, oxidative stress, hypoxia, and inflammation to improve diabetic fracture healing. The innovative biomaterial promotes bone regeneration in diabetic rats.
Area of Science:
- Biomaterials Science
- Regenerative Medicine
- Diabetic Complications
Background:
- Diabetes mellitus impairs fracture healing via hyperglycemia, oxidative stress, hypoxia, and inflammation.
- Existing biomaterials often target only one pathological factor, failing to address the complex diabetic fracture microenvironment.
- A multi-targeted approach is crucial for effective diabetic bone repair.
Purpose of the Study:
- To develop a nanozyme-integrated hydrogel (Gel-FQG) for simultaneous regulation of hyperglycemia, oxidative stress, hypoxia, and immune imbalance in diabetic fractures.
- To investigate the therapeutic potential of Gel-FQG in promoting vascularized bone regeneration and fracture healing in a diabetic rat model.
Main Methods:
- Development of a Gel-FQG incorporating glucose oxidase (GOx)-loaded Fe3+-quercetin nanozymes within a dynamic Schiff-base hydrogel.
- In vitro assessment of Gel-FQG's effects on oxidative stress, hypoxia, macrophage polarization, and osteogenic/angiogenic responses under hyperglycemic conditions.
- In vivo evaluation of Gel-FQG in a diabetic rat femoral fracture model to assess bone regeneration and healing.
Main Results:
- Gel-FQG effectively consumed glucose, scavenged reactive oxygen species (ROS), and generated oxygen, disrupting the pathological feedback loop.
- In vitro studies showed Gel-FQG alleviated oxidative stress and hypoxia, promoted M2 macrophage polarization, and enhanced osteogenesis and angiogenesis.
- Local implantation of Gel-FQG significantly accelerated vascularized bone regeneration and fracture healing in diabetic rats.
Conclusions:
- Gel-FQG actively remodels the diabetic fracture microenvironment by simultaneously targeting multiple pathological factors.
- This nanozyme-integrated hydrogel represents a promising therapeutic strategy for enhancing diabetic bone repair and fracture healing.
