Lemon-derived nanoparticle-functionalized hydrogels regulate macrophage reprogramming to promote diabetic wound healing

Abstract The orderly regulation of immune inflammation and promotion of the regeneration of skin vessels and fibers are key to the treatment of diabetic skin injury (DSI). Although various traditional polypeptide biological dressings continue to be developed, their efficacy is not satisfactory. In r...

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Main Authors: Enyou Jin, Yusheng Yang, Shengjie Cong, Dengke Chen, Ruixiong Chen, Jun Zhang, Yanjun Hu, Weini Chen
Format: Article
Language:English
Published: BMC 2025-01-01
Series:Journal of Nanobiotechnology
Subjects:
Online Access:https://doi.org/10.1186/s12951-025-03138-y
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author Enyou Jin
Yusheng Yang
Shengjie Cong
Dengke Chen
Ruixiong Chen
Jun Zhang
Yanjun Hu
Weini Chen
author_facet Enyou Jin
Yusheng Yang
Shengjie Cong
Dengke Chen
Ruixiong Chen
Jun Zhang
Yanjun Hu
Weini Chen
author_sort Enyou Jin
collection DOAJ
description Abstract The orderly regulation of immune inflammation and promotion of the regeneration of skin vessels and fibers are key to the treatment of diabetic skin injury (DSI). Although various traditional polypeptide biological dressings continue to be developed, their efficacy is not satisfactory. In recent years, plant-to-mammal regulation has provided an effective approach for chronic wound management, but the development of effective plant-based treatments remains challenging. The development of exosomes from Chinese herbs is promising for wound healing. In this study, plant exosomes derived from lemons (Citrus limon) were extracted, and their biological efficacy was verified. Lemon exosomes regulated the polarization reprogramming of macrophages, promoted the proliferation and migration of vascular endothelial cells and fibroblasts, and thus promoted the healing of diabetic wounds. To solve the problems of continuous drug delivery and penetration depth, Lemon Exosomes were loaded into a hydrogel constructed of Gelatin Methacryloyl (GelMA) and Dialdehyde Starch (DAS) that closely fits to the skin, absorbs water, swells, and is moist and breathable, effectively promoting the sustained and slow release of exosomes and resulting in excellent performance for diabetic wound healing. Our GelMA-DAS-Lemon Exosomes hydrogel (GelMA/DAS/Exo hydrogel) patch represents a potentially valuable option for repairing diabetic wounds in clinical applications. Graphical Abstracts
format Article
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institution Kabale University
issn 1477-3155
language English
publishDate 2025-01-01
publisher BMC
record_format Article
series Journal of Nanobiotechnology
spelling doaj-art-38933f26b2f04262a138bc3ab9a4f5db2025-02-02T12:41:03ZengBMCJournal of Nanobiotechnology1477-31552025-01-0123112510.1186/s12951-025-03138-yLemon-derived nanoparticle-functionalized hydrogels regulate macrophage reprogramming to promote diabetic wound healingEnyou Jin0Yusheng Yang1Shengjie Cong2Dengke Chen3Ruixiong Chen4Jun Zhang5Yanjun Hu6Weini Chen7Faculty of Chinese Medicine, Macau University of Science and TechnologyDivision of Orthopedics and Traumatology, Department of Orthopedics, Nanfang Hospital, Southern Medical UniversityChangchun University of Chinese MedicineFaculty of Chinese Medicine, Macau University of Science and TechnologyDepartment of Orthopedics, The First People’s Hospital of HuizhouFaculty of Chinese Medicine, Macau University of Science and TechnologyDivision of Orthopedics and Traumatology, Department of Orthopedics, Nanfang Hospital, Southern Medical UniversityFaculty of Chinese Medicine, Macau University of Science and TechnologyAbstract The orderly regulation of immune inflammation and promotion of the regeneration of skin vessels and fibers are key to the treatment of diabetic skin injury (DSI). Although various traditional polypeptide biological dressings continue to be developed, their efficacy is not satisfactory. In recent years, plant-to-mammal regulation has provided an effective approach for chronic wound management, but the development of effective plant-based treatments remains challenging. The development of exosomes from Chinese herbs is promising for wound healing. In this study, plant exosomes derived from lemons (Citrus limon) were extracted, and their biological efficacy was verified. Lemon exosomes regulated the polarization reprogramming of macrophages, promoted the proliferation and migration of vascular endothelial cells and fibroblasts, and thus promoted the healing of diabetic wounds. To solve the problems of continuous drug delivery and penetration depth, Lemon Exosomes were loaded into a hydrogel constructed of Gelatin Methacryloyl (GelMA) and Dialdehyde Starch (DAS) that closely fits to the skin, absorbs water, swells, and is moist and breathable, effectively promoting the sustained and slow release of exosomes and resulting in excellent performance for diabetic wound healing. Our GelMA-DAS-Lemon Exosomes hydrogel (GelMA/DAS/Exo hydrogel) patch represents a potentially valuable option for repairing diabetic wounds in clinical applications. Graphical Abstractshttps://doi.org/10.1186/s12951-025-03138-yDiabetic wound healingMacrophage reprogrammingLemon exosomesAngiogenesisNetwork pharmacology
spellingShingle Enyou Jin
Yusheng Yang
Shengjie Cong
Dengke Chen
Ruixiong Chen
Jun Zhang
Yanjun Hu
Weini Chen
Lemon-derived nanoparticle-functionalized hydrogels regulate macrophage reprogramming to promote diabetic wound healing
Journal of Nanobiotechnology
Diabetic wound healing
Macrophage reprogramming
Lemon exosomes
Angiogenesis
Network pharmacology
title Lemon-derived nanoparticle-functionalized hydrogels regulate macrophage reprogramming to promote diabetic wound healing
title_full Lemon-derived nanoparticle-functionalized hydrogels regulate macrophage reprogramming to promote diabetic wound healing
title_fullStr Lemon-derived nanoparticle-functionalized hydrogels regulate macrophage reprogramming to promote diabetic wound healing
title_full_unstemmed Lemon-derived nanoparticle-functionalized hydrogels regulate macrophage reprogramming to promote diabetic wound healing
title_short Lemon-derived nanoparticle-functionalized hydrogels regulate macrophage reprogramming to promote diabetic wound healing
title_sort lemon derived nanoparticle functionalized hydrogels regulate macrophage reprogramming to promote diabetic wound healing
topic Diabetic wound healing
Macrophage reprogramming
Lemon exosomes
Angiogenesis
Network pharmacology
url https://doi.org/10.1186/s12951-025-03138-y
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