Probiotic active gel promotes diabetic wound healing through continuous local glucose consumption and antioxidant

Abstract Background Diabetic foot ulcers (DFU) are severe complications of diabetes, posing significant health and societal challenges. Accumulation of reactive oxygen species (ROS) and elevated glucose levels are primary factors affecting diabetic wound healing. Achieving effective treatment by red...

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Main Authors: Yingshuai Wang, Lihua Shi, Junna Lu, Fengyuan Wang, Zihan Zhou, Yuexuan Wang, Xiangyu Du, Di Qin, Fangman Chen, Dan Shao, Yuanyuan Gao, Cheng Gao, Tongyi Sun
Format: Article
Language:English
Published: BMC 2025-01-01
Series:Journal of Nanobiotechnology
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Online Access:https://doi.org/10.1186/s12951-025-03115-5
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author Yingshuai Wang
Lihua Shi
Junna Lu
Fengyuan Wang
Zihan Zhou
Yuexuan Wang
Xiangyu Du
Di Qin
Fangman Chen
Dan Shao
Yuanyuan Gao
Cheng Gao
Tongyi Sun
author_facet Yingshuai Wang
Lihua Shi
Junna Lu
Fengyuan Wang
Zihan Zhou
Yuexuan Wang
Xiangyu Du
Di Qin
Fangman Chen
Dan Shao
Yuanyuan Gao
Cheng Gao
Tongyi Sun
author_sort Yingshuai Wang
collection DOAJ
description Abstract Background Diabetic foot ulcers (DFU) are severe complications of diabetes, posing significant health and societal challenges. Accumulation of reactive oxygen species (ROS) and elevated glucose levels are primary factors affecting diabetic wound healing. Achieving effective treatment by reducing ROS alone is challenging, as high glucose levels continuously drive ROS production. The excellent glucose-consuming capacity of lactobacilli and the antioxidant function of hydrogen undoubtedly provide good therapeutic ideas. Herein, we combined probiotic Lactobacillus reuteri with acid-responsive hydrogen-producing nanoparticles to construct probiotic active gel LR&AB@CAH to enable a cascade of glucose consumption and hydrogen production. Lactobacillus reuteri consumed overproduced glucose and thereby released lactic acid to activate nanoparticle for hydrogen production, which could neutralize excess ROS and promote wound healing. Results In vitro experiments demonstrate that LR&AB@CAH has good biocompatibility, antioxidant capacity. LR&AB@CAH reduces excess ROS, decreases oxidative substances, and boosts antioxidant enzyme activity. In a diabetic wound mouse model, it functions as a glucose scavenger and antioxidant, reducing ROS and supporting wound healing. Conclusion LR&AB@CAH offers a novel strategy for the comprehensive treatment of DFU. This study provides an artificial-natural composite hydrogel for cascade therapy on diabetic wound healing, and suggests a complete management approach for diabetic oxidative stress.
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spelling doaj-art-7bf6ed38a1434fd9b30b8156c797c1c82025-02-02T12:41:10ZengBMCJournal of Nanobiotechnology1477-31552025-01-0123112110.1186/s12951-025-03115-5Probiotic active gel promotes diabetic wound healing through continuous local glucose consumption and antioxidantYingshuai Wang0Lihua Shi1Junna Lu2Fengyuan Wang3Zihan Zhou4Yuexuan Wang5Xiangyu Du6Di Qin7Fangman Chen8Dan Shao9Yuanyuan Gao10Cheng Gao11Tongyi Sun12Shandong Key Laboratory of Proteins and Peptides Pharmaceutical Engineering, Shandong Universities Key Laboratory of Biological Medicine, School of Life Science and Technology, Shandong Second Medical UniversityShandong Key Laboratory of Proteins and Peptides Pharmaceutical Engineering, Shandong Universities Key Laboratory of Biological Medicine, School of Life Science and Technology, Shandong Second Medical UniversitySchool of Biomedical Sciences and Engineering, South China University of TechnologyShandong Key Laboratory of Proteins and Peptides Pharmaceutical Engineering, Shandong Universities Key Laboratory of Biological Medicine, School of Life Science and Technology, Shandong Second Medical UniversityShandong Key Laboratory of Proteins and Peptides Pharmaceutical Engineering, Shandong Universities Key Laboratory of Biological Medicine, School of Life Science and Technology, Shandong Second Medical UniversityShandong Key Laboratory of Proteins and Peptides Pharmaceutical Engineering, Shandong Universities Key Laboratory of Biological Medicine, School of Life Science and Technology, Shandong Second Medical UniversityShandong Key Laboratory of Proteins and Peptides Pharmaceutical Engineering, Shandong Universities Key Laboratory of Biological Medicine, School of Life Science and Technology, Shandong Second Medical UniversityShandong Key Laboratory of Proteins and Peptides Pharmaceutical Engineering, Shandong Universities Key Laboratory of Biological Medicine, School of Life Science and Technology, Shandong Second Medical UniversitySchool of Biomedical Sciences and Engineering, South China University of TechnologySchool of Biomedical Sciences and Engineering, South China University of TechnologySchool of Pharmacy, Shandong Second Medical UniversitySchool of Pharmacy, Shenzhen University Medical School, Shenzhen UniversityShandong Key Laboratory of Proteins and Peptides Pharmaceutical Engineering, Shandong Universities Key Laboratory of Biological Medicine, School of Life Science and Technology, Shandong Second Medical UniversityAbstract Background Diabetic foot ulcers (DFU) are severe complications of diabetes, posing significant health and societal challenges. Accumulation of reactive oxygen species (ROS) and elevated glucose levels are primary factors affecting diabetic wound healing. Achieving effective treatment by reducing ROS alone is challenging, as high glucose levels continuously drive ROS production. The excellent glucose-consuming capacity of lactobacilli and the antioxidant function of hydrogen undoubtedly provide good therapeutic ideas. Herein, we combined probiotic Lactobacillus reuteri with acid-responsive hydrogen-producing nanoparticles to construct probiotic active gel LR&AB@CAH to enable a cascade of glucose consumption and hydrogen production. Lactobacillus reuteri consumed overproduced glucose and thereby released lactic acid to activate nanoparticle for hydrogen production, which could neutralize excess ROS and promote wound healing. Results In vitro experiments demonstrate that LR&AB@CAH has good biocompatibility, antioxidant capacity. LR&AB@CAH reduces excess ROS, decreases oxidative substances, and boosts antioxidant enzyme activity. In a diabetic wound mouse model, it functions as a glucose scavenger and antioxidant, reducing ROS and supporting wound healing. Conclusion LR&AB@CAH offers a novel strategy for the comprehensive treatment of DFU. This study provides an artificial-natural composite hydrogel for cascade therapy on diabetic wound healing, and suggests a complete management approach for diabetic oxidative stress.https://doi.org/10.1186/s12951-025-03115-5Diabetic woundHyperglycemiaOxidative stressGlucose-consuming and hydrogen releaseProbiotic active gel
spellingShingle Yingshuai Wang
Lihua Shi
Junna Lu
Fengyuan Wang
Zihan Zhou
Yuexuan Wang
Xiangyu Du
Di Qin
Fangman Chen
Dan Shao
Yuanyuan Gao
Cheng Gao
Tongyi Sun
Probiotic active gel promotes diabetic wound healing through continuous local glucose consumption and antioxidant
Journal of Nanobiotechnology
Diabetic wound
Hyperglycemia
Oxidative stress
Glucose-consuming and hydrogen release
Probiotic active gel
title Probiotic active gel promotes diabetic wound healing through continuous local glucose consumption and antioxidant
title_full Probiotic active gel promotes diabetic wound healing through continuous local glucose consumption and antioxidant
title_fullStr Probiotic active gel promotes diabetic wound healing through continuous local glucose consumption and antioxidant
title_full_unstemmed Probiotic active gel promotes diabetic wound healing through continuous local glucose consumption and antioxidant
title_short Probiotic active gel promotes diabetic wound healing through continuous local glucose consumption and antioxidant
title_sort probiotic active gel promotes diabetic wound healing through continuous local glucose consumption and antioxidant
topic Diabetic wound
Hyperglycemia
Oxidative stress
Glucose-consuming and hydrogen release
Probiotic active gel
url https://doi.org/10.1186/s12951-025-03115-5
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