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Phospholipid-grafted PLLA electrospun micro/nanofibers immobilized with small extracellular vesicles from rat adipose mesenchymal stem cells promote wound healing in diabetic rats

Small extracellular vesicles (sEVs) derived from mesenchymal stem cells (MSCs) can deliver a variety of bioactive factors to create a favorable local microenvironment, thereby holding huge potential in chronic wound repair. However, free sEVs administrated intravenously or locally are usually cleare...

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Autores principales: Li, Jing, Yan, Shunshun, Han, Weiju, Dong, Zixuan, Li, Junliang, Wu, Qi, Fu, Xiaoling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9555996/
https://www.ncbi.nlm.nih.gov/pubmed/36246766
http://dx.doi.org/10.1093/rb/rbac071
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author Li, Jing
Yan, Shunshun
Han, Weiju
Dong, Zixuan
Li, Junliang
Wu, Qi
Fu, Xiaoling
author_facet Li, Jing
Yan, Shunshun
Han, Weiju
Dong, Zixuan
Li, Junliang
Wu, Qi
Fu, Xiaoling
author_sort Li, Jing
collection PubMed
description Small extracellular vesicles (sEVs) derived from mesenchymal stem cells (MSCs) can deliver a variety of bioactive factors to create a favorable local microenvironment, thereby holding huge potential in chronic wound repair. However, free sEVs administrated intravenously or locally are usually cleared rapidly, resulting in an insufficient duration of the efficacy. Thus, strategies that enable optimized retention and release profiles of sEVs at wound sites are desirable. Herein, we fabricated novel functional phosphoethanolamine phospholipid-grafted poly-l-lactic acid micro/nanofibers (DSPE-PLLA) to carry and retain sEVs from rat adipose MSCs, enabling the slow local release of sEVs. Our results showed that sEVs@DSPE-PLLA promoted the proliferation, migration and gene expression (Col I, Col III, TGF-β, α-SMA, HIF-1α) of fibroblasts. It also promoted keratinocyte proliferation. In addition, sEVs@DSPE-PLLA helped polarize macrophages toward the M2 phenotype by increasing the expression of anti-inflammatory genes (Arginase 1, CD 206, IL-10) and inhibiting the expression of pro-inflammatory genes (IL-1β, TNF-α). Further in vivo study in diabetic rat models showed that sEVs@DSPE-PLLA improved the wound-healing process by alleviating the inflammatory responses, stimulating cell proliferation, collagen deposition and angiogenesis. These results highlight the potential of using DSPE-grafted scaffolds for extracellular vesicle immobilization and suggest sEVs@DSPE-PLLA micro/nanofibers as promising functional wound dressings for diabetic wounds.
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spelling pubmed-95559962022-10-13 Phospholipid-grafted PLLA electrospun micro/nanofibers immobilized with small extracellular vesicles from rat adipose mesenchymal stem cells promote wound healing in diabetic rats Li, Jing Yan, Shunshun Han, Weiju Dong, Zixuan Li, Junliang Wu, Qi Fu, Xiaoling Regen Biomater Research Article Small extracellular vesicles (sEVs) derived from mesenchymal stem cells (MSCs) can deliver a variety of bioactive factors to create a favorable local microenvironment, thereby holding huge potential in chronic wound repair. However, free sEVs administrated intravenously or locally are usually cleared rapidly, resulting in an insufficient duration of the efficacy. Thus, strategies that enable optimized retention and release profiles of sEVs at wound sites are desirable. Herein, we fabricated novel functional phosphoethanolamine phospholipid-grafted poly-l-lactic acid micro/nanofibers (DSPE-PLLA) to carry and retain sEVs from rat adipose MSCs, enabling the slow local release of sEVs. Our results showed that sEVs@DSPE-PLLA promoted the proliferation, migration and gene expression (Col I, Col III, TGF-β, α-SMA, HIF-1α) of fibroblasts. It also promoted keratinocyte proliferation. In addition, sEVs@DSPE-PLLA helped polarize macrophages toward the M2 phenotype by increasing the expression of anti-inflammatory genes (Arginase 1, CD 206, IL-10) and inhibiting the expression of pro-inflammatory genes (IL-1β, TNF-α). Further in vivo study in diabetic rat models showed that sEVs@DSPE-PLLA improved the wound-healing process by alleviating the inflammatory responses, stimulating cell proliferation, collagen deposition and angiogenesis. These results highlight the potential of using DSPE-grafted scaffolds for extracellular vesicle immobilization and suggest sEVs@DSPE-PLLA micro/nanofibers as promising functional wound dressings for diabetic wounds. Oxford University Press 2022-09-26 /pmc/articles/PMC9555996/ /pubmed/36246766 http://dx.doi.org/10.1093/rb/rbac071 Text en © The Author(s) 2022. Published by Oxford University Press. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Li, Jing
Yan, Shunshun
Han, Weiju
Dong, Zixuan
Li, Junliang
Wu, Qi
Fu, Xiaoling
Phospholipid-grafted PLLA electrospun micro/nanofibers immobilized with small extracellular vesicles from rat adipose mesenchymal stem cells promote wound healing in diabetic rats
title Phospholipid-grafted PLLA electrospun micro/nanofibers immobilized with small extracellular vesicles from rat adipose mesenchymal stem cells promote wound healing in diabetic rats
title_full Phospholipid-grafted PLLA electrospun micro/nanofibers immobilized with small extracellular vesicles from rat adipose mesenchymal stem cells promote wound healing in diabetic rats
title_fullStr Phospholipid-grafted PLLA electrospun micro/nanofibers immobilized with small extracellular vesicles from rat adipose mesenchymal stem cells promote wound healing in diabetic rats
title_full_unstemmed Phospholipid-grafted PLLA electrospun micro/nanofibers immobilized with small extracellular vesicles from rat adipose mesenchymal stem cells promote wound healing in diabetic rats
title_short Phospholipid-grafted PLLA electrospun micro/nanofibers immobilized with small extracellular vesicles from rat adipose mesenchymal stem cells promote wound healing in diabetic rats
title_sort phospholipid-grafted plla electrospun micro/nanofibers immobilized with small extracellular vesicles from rat adipose mesenchymal stem cells promote wound healing in diabetic rats
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9555996/
https://www.ncbi.nlm.nih.gov/pubmed/36246766
http://dx.doi.org/10.1093/rb/rbac071
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