A novel hydrogel loaded with plant exosomes and stem cell exosomes as a new strategy for treating diabetic wounds

Diabetic wound healing is constrained by various factors, including chronic inflammation, sustained oxidative stress, impaired angiogenesis, and abnormal wound microenvironments. Exosomes derived from mesenchymal stem cells (MSC-exo) contain a wealth of bioactive substances that play a positive role...

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Main Authors: Jialu Weng, Yizhang Chen, Yuhan Zeng, Wenzhang Jin, Ying Ji, Wa Zhang, Shunfu Wang, Haobing Li, Meilin Yi, Xiaoying Niu, Xuchen Deng, Jiancheng Huang, Xiang Su, Lulu Chen
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Language:English
Published: Elsevier 2025-06-01
Series:Materials Today Bio
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Online Access:http://www.sciencedirect.com/science/article/pii/S2590006425003709
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author Jialu Weng
Yizhang Chen
Yuhan Zeng
Wenzhang Jin
Ying Ji
Wa Zhang
Shunfu Wang
Haobing Li
Meilin Yi
Xiaoying Niu
Xuchen Deng
Jiancheng Huang
Xiang Su
Lulu Chen
author_facet Jialu Weng
Yizhang Chen
Yuhan Zeng
Wenzhang Jin
Ying Ji
Wa Zhang
Shunfu Wang
Haobing Li
Meilin Yi
Xiaoying Niu
Xuchen Deng
Jiancheng Huang
Xiang Su
Lulu Chen
author_sort Jialu Weng
collection DOAJ
description Diabetic wound healing is constrained by various factors, including chronic inflammation, sustained oxidative stress, impaired angiogenesis, and abnormal wound microenvironments. Exosomes derived from mesenchymal stem cells (MSC-exo) contain a wealth of bioactive substances that play a positive role in promoting diabetic wound healing. Plant-derived exosomes, as a novel therapeutic approach, are continuously being explored. Momordica charantia (MC) has been shown to possess blood glucose-lowering effects, and its exosomes are of significant relevance for treating diabetic wounds. However, direct application of exosomes to wounds faces challenges such as poor stability and short retention time, limiting their therapeutic effectiveness and clinical applicability. Encapsulating exosomes in hydrogels is an effective strategy to preserve their bioactivity. In this study, we fabricated a hydrogel loaded with MSC-exo and MC exosomes (MC-exo) by photopolymerization of methacrylated gelatin (GelMA) and dopamine (MEMC-Gel). The resulting MEMC-Gel exhibited favorable mechanical properties, adhesion, degradability, absorbency, and biocompatibility. In vitro, MEMC-Gel demonstrated the ability to resist inflammation, counter oxidative stress, promote fibroblast migration, support endothelial cell angiogenesis, and regulate macrophage polarization. In a diabetic mouse wound model, MEMC-Gel accelerated wound healing by inhibiting inflammation and oxidative stress, modulating macrophage immune responses and hyperglycemia within the microenvironment, promoting angiogenesis, and enhancing epithelialization. In conclusion, MEMC-Gel is an outstanding hydrogel dressing that synergistically promotes repair by loading MSC-exo and MC-exo, significantly accelerating diabetic wound healing through multiple mechanisms. This multifunctional hydrogel, based on exosomes from two different sources, provides an innovative therapeutic strategy for diabetic wound repair with broad clinical application potential.
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spelling doaj-art-8cf4576f404b487f811e036ad2341a4e2025-08-20T01:55:52ZengElsevierMaterials Today Bio2590-00642025-06-013210181010.1016/j.mtbio.2025.101810A novel hydrogel loaded with plant exosomes and stem cell exosomes as a new strategy for treating diabetic woundsJialu Weng0Yizhang Chen1Yuhan Zeng2Wenzhang Jin3Ying Ji4Wa Zhang5Shunfu Wang6Haobing Li7Meilin Yi8Xiaoying Niu9Xuchen Deng10Jiancheng Huang11Xiang Su12Lulu Chen13Department of Anesthesia, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, PR China; Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, PR ChinaKey Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, PR China; School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325000, PR ChinaDepartment of Anesthesia, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, PR China; Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, PR China; School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325000, PR ChinaDepartment of Anesthesia, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, PR China; Department of Colorectal Surgery, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310000, PR China; Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, PR China; Corresponding authors. Department of Colorectal Surgery, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310000, PR China.Department of Nephrology, The First Affiliated Hospital of Ningbo University, Ningbo, 315010, PR ChinaDepartment of Colorectal Surgery, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310000, PR China; Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, PR ChinaDepartment of Anesthesia, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, PR China; Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, PR ChinaKey Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, PR ChinaKey Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, PR ChinaKey Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, PR ChinaKey Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, PR ChinaDepartment of Nephrology, The First Affiliated Hospital of Ningbo University, Ningbo, 315010, PR China; Corresponding author. Department of Nephrology, The First Affiliated Hospital of Ningbo University, Ningbo, 315010, PR China.Department of Anesthesia, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, PR China; Department of Vascular Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, PR China; Corresponding authors. Department of Vascular Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, PR China.Department of Anesthesia, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, PR China; Department of Vascular Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, PR China; Corresponding author. Department of Anesthesia, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, PR China.Diabetic wound healing is constrained by various factors, including chronic inflammation, sustained oxidative stress, impaired angiogenesis, and abnormal wound microenvironments. Exosomes derived from mesenchymal stem cells (MSC-exo) contain a wealth of bioactive substances that play a positive role in promoting diabetic wound healing. Plant-derived exosomes, as a novel therapeutic approach, are continuously being explored. Momordica charantia (MC) has been shown to possess blood glucose-lowering effects, and its exosomes are of significant relevance for treating diabetic wounds. However, direct application of exosomes to wounds faces challenges such as poor stability and short retention time, limiting their therapeutic effectiveness and clinical applicability. Encapsulating exosomes in hydrogels is an effective strategy to preserve their bioactivity. In this study, we fabricated a hydrogel loaded with MSC-exo and MC exosomes (MC-exo) by photopolymerization of methacrylated gelatin (GelMA) and dopamine (MEMC-Gel). The resulting MEMC-Gel exhibited favorable mechanical properties, adhesion, degradability, absorbency, and biocompatibility. In vitro, MEMC-Gel demonstrated the ability to resist inflammation, counter oxidative stress, promote fibroblast migration, support endothelial cell angiogenesis, and regulate macrophage polarization. In a diabetic mouse wound model, MEMC-Gel accelerated wound healing by inhibiting inflammation and oxidative stress, modulating macrophage immune responses and hyperglycemia within the microenvironment, promoting angiogenesis, and enhancing epithelialization. In conclusion, MEMC-Gel is an outstanding hydrogel dressing that synergistically promotes repair by loading MSC-exo and MC-exo, significantly accelerating diabetic wound healing through multiple mechanisms. This multifunctional hydrogel, based on exosomes from two different sources, provides an innovative therapeutic strategy for diabetic wound repair with broad clinical application potential.http://www.sciencedirect.com/science/article/pii/S2590006425003709Momordica charantiaMesenchymal stem cellExosomesHydrogelDiabetic wounds
spellingShingle Jialu Weng
Yizhang Chen
Yuhan Zeng
Wenzhang Jin
Ying Ji
Wa Zhang
Shunfu Wang
Haobing Li
Meilin Yi
Xiaoying Niu
Xuchen Deng
Jiancheng Huang
Xiang Su
Lulu Chen
A novel hydrogel loaded with plant exosomes and stem cell exosomes as a new strategy for treating diabetic wounds
Materials Today Bio
Momordica charantia
Mesenchymal stem cell
Exosomes
Hydrogel
Diabetic wounds
title A novel hydrogel loaded with plant exosomes and stem cell exosomes as a new strategy for treating diabetic wounds
title_full A novel hydrogel loaded with plant exosomes and stem cell exosomes as a new strategy for treating diabetic wounds
title_fullStr A novel hydrogel loaded with plant exosomes and stem cell exosomes as a new strategy for treating diabetic wounds
title_full_unstemmed A novel hydrogel loaded with plant exosomes and stem cell exosomes as a new strategy for treating diabetic wounds
title_short A novel hydrogel loaded with plant exosomes and stem cell exosomes as a new strategy for treating diabetic wounds
title_sort novel hydrogel loaded with plant exosomes and stem cell exosomes as a new strategy for treating diabetic wounds
topic Momordica charantia
Mesenchymal stem cell
Exosomes
Hydrogel
Diabetic wounds
url http://www.sciencedirect.com/science/article/pii/S2590006425003709
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