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Updated: Jul 25, 2026
Protocol to Create Chronic Wounds in Diabetic Mice
Published on: September 25, 2019
Zn-DHM nanozymes regulate metabolic and immune homeostasis for early diabetic wound therapy
Shuo Zhang1, Xinyu Zhao1, Wei Zhang2
1Department of Burns, The First Affiliated Hospital of Anhui Medical University, Hefei, 230032, PR China.
Abstract:
Diabetic wounds heal slowly or incompletely because of the microenvironment of hyperglycemia, high levels of reactive oxygen species (ROS), excessive inflammation, metabolic disorders and immune dysregulation, and the therapeutic effect is limited only by disruption of the reactive oxygen species (ROS)-inflammation cascade cycle. Here, a novel metal-polyphenolic nanozyme (Zn-DHM NPs) synthesized by the coordination of Zn2+ with dihydromyricetin (DHM) was designed, which not only has a superior ability to scavenge ROS and promote cell proliferation and migration but also functions in the regulation of metabolism and immune homeostasis. In vitro and in vivo experiments and RNA sequencing analyses revealed that Zn-DHM NPs could increase the levels of intracellular SOD and CAT enzymes to scavenge ROS and maintain the level of the mitochondrial membrane potential to reduce apoptosis. In terms of glucose metabolism, Zn-DHM NPs downregulated excessive levels of intracellular glucose and HK2, inhibited excessive glycolysis and downregulated the AGE-RAGE pathway to restore cellular function. In terms of immune regulation, Zn-DHM NPs not only downregulate M1/M2 levels to promote tissue repair but also maintain Th17/Treg homeostasis, downregulate the IL-17 signaling pathway to reduce inflammation, and upregulate FOXP3 to maintain immune homeostasis, thereby promoting early wound healing in diabetic mice. The development of Zn-DHM NPs provides a new therapeutic target to promote early healing of diabetic wounds.
Insights
A novel nanozyme, Zn-DHM NPs, effectively scavenges reactive oxygen species (ROS) and regulates metabolism and immune responses, promoting early wound healing in diabetic mice.
Area of Science:
- Biomaterials Science
- Nanomedicine
- Wound Healing Research
Background:
- Diabetic wounds exhibit impaired healing due to hyperglycemia, oxidative stress, inflammation, and immune dysregulation.
- Current therapies are limited by their inability to disrupt the reactive oxygen species (ROS)-inflammation cascade.
- Targeting this cycle is crucial for enhancing diabetic wound repair.
Purpose of the Study:
- To develop and evaluate a novel metal-polyphenolic nanozyme (Zn-DHM NPs) for promoting diabetic wound healing.
- To investigate the mechanisms underlying Zn-DHM NPs' therapeutic effects on ROS scavenging, metabolism, and immune homeostasis.
- To assess the efficacy of Zn-DHM NPs in an *in vivo* diabetic wound model.
Main Methods:
- Synthesis of Zn-DHM NPs via coordination of Zn2+ with dihydromyricetin (DHM).
- In vitro and in vivo experiments, including cell proliferation, migration assays, and wound healing studies in diabetic mice.
- RNA sequencing analysis to elucidate molecular mechanisms, including ROS scavenging, glucose metabolism, and immune regulation pathways.
Main Results:
- Zn-DHM NPs demonstrated superior ROS scavenging by increasing SOD and CAT enzyme levels and maintaining mitochondrial membrane potential.
- The nanozyme regulated glucose metabolism by downregulating intracellular glucose, HK2, glycolysis, and the AGE-RAGE pathway.
- Zn-DHM NPs modulated immune responses, downregulating M1/M2 and IL-17 signaling while upregulating FOXP3, promoting tissue repair and immune homeostasis.
Conclusions:
- Zn-DHM NPs represent a promising therapeutic strategy for accelerating early wound healing in diabetic conditions.
- The nanozyme's multifaceted action on oxidative stress, metabolism, and immunity offers a novel approach to combatting diabetic wound complications.
- Further development of Zn-DHM NPs could lead to new therapeutic targets for diabetic wound management.
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