Regulation of inflammatory microenvironment using a self-healing hydrogel loaded with BM-MSCs for advanced wound healing in rat diabetic foot ulcers

A diabetic foot ulcer (DFUs) is a state of prolonged chronic inflammation, which can result in amputation. Different from normal skin wounds, various commercially available dressings have not sufficiently improved the healing of DFUs. In this study, a novel self-healing hydrogel was prepared by in s...

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Main Authors: Haotian Bai, Noh Kyu-Cheol, Zhonghan Wang, Yutao Cui, He Liu, Hou Liu, Yubin Feng, Yue Zhao, Quan Lin, Zuhao Li
Format: Article
Language:English
Published: SAGE Publishing 2020-07-01
Series:Journal of Tissue Engineering
Online Access:https://doi.org/10.1177/2041731420947242
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author Haotian Bai
Noh Kyu-Cheol
Zhonghan Wang
Yutao Cui
He Liu
Hou Liu
Yubin Feng
Yue Zhao
Quan Lin
Zuhao Li
author_facet Haotian Bai
Noh Kyu-Cheol
Zhonghan Wang
Yutao Cui
He Liu
Hou Liu
Yubin Feng
Yue Zhao
Quan Lin
Zuhao Li
author_sort Haotian Bai
collection DOAJ
description A diabetic foot ulcer (DFUs) is a state of prolonged chronic inflammation, which can result in amputation. Different from normal skin wounds, various commercially available dressings have not sufficiently improved the healing of DFUs. In this study, a novel self-healing hydrogel was prepared by in situ crosslinking of N -carboxyethyl chitosan ( N -chitosan) and adipic acid dihydrazide (ADH) with hyaluronic acid-aldehyde (HA-ALD), to provide a moist and inflammatory relief environment to promote stem cell proliferation or secretion of growth factors, thus accelerating wound healing. The results demonstrated that this injectable and self-healing hydrogel has excellent swelling properties, stability, and mechanical properties. This biocompatible hydrogel stimulated secretion of growth factors from bone marrow mesenchymal stem cells (BM-MSCs) and regulated the inflammatory environment by inhibiting the expression of M1 macrophages and promoting the expression of M2 macrophages, resulting in granulation tissue formation, collagen deposition, nucleated cell proliferation, neovascularization, and enhanced diabetic wound healing. This study showed that N -chitosan/HA-ALD hydrogel could be used as a multifunctional injectable wound dressing to regulate chronic inflammation and provide an optimal environment for BM-MSCs to promote diabetic wound healing.
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spelling doaj.art-fe1ac73613e44c45beaa958114935a482022-12-22T02:24:24ZengSAGE PublishingJournal of Tissue Engineering2041-73142020-07-011110.1177/2041731420947242Regulation of inflammatory microenvironment using a self-healing hydrogel loaded with BM-MSCs for advanced wound healing in rat diabetic foot ulcersHaotian Bai0Noh Kyu-Cheol1Zhonghan Wang2Yutao Cui3He Liu4Hou Liu5Yubin Feng6Yue Zhao7Quan Lin8Zuhao Li9Department of Orthopedics, Hallym University, Chuncheon, Gangwon-do, KoreaDepartment of Orthopedics, Hallym University, Chuncheon, Gangwon-do, KoreaDepartment of Orthopedics, The Second Hospital of Jilin University, Changchun, Jilin, P. R. ChinaDepartment of Orthopedics, The Second Hospital of Jilin University, Changchun, Jilin, P. R. ChinaDepartment of Orthopedics, The Second Hospital of Jilin University, Changchun, Jilin, P. R. ChinaState Key Lab of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun, Jilin, P. R. ChinaState Key Lab of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun, Jilin, P. R. ChinaState Key Lab of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun, Jilin, P. R. ChinaState Key Lab of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun, Jilin, P. R. ChinaDepartment of Pain, Renji Hospital, South Campus, Shanghai Jiaotong University, Shanghai, P. R. ChinaA diabetic foot ulcer (DFUs) is a state of prolonged chronic inflammation, which can result in amputation. Different from normal skin wounds, various commercially available dressings have not sufficiently improved the healing of DFUs. In this study, a novel self-healing hydrogel was prepared by in situ crosslinking of N -carboxyethyl chitosan ( N -chitosan) and adipic acid dihydrazide (ADH) with hyaluronic acid-aldehyde (HA-ALD), to provide a moist and inflammatory relief environment to promote stem cell proliferation or secretion of growth factors, thus accelerating wound healing. The results demonstrated that this injectable and self-healing hydrogel has excellent swelling properties, stability, and mechanical properties. This biocompatible hydrogel stimulated secretion of growth factors from bone marrow mesenchymal stem cells (BM-MSCs) and regulated the inflammatory environment by inhibiting the expression of M1 macrophages and promoting the expression of M2 macrophages, resulting in granulation tissue formation, collagen deposition, nucleated cell proliferation, neovascularization, and enhanced diabetic wound healing. This study showed that N -chitosan/HA-ALD hydrogel could be used as a multifunctional injectable wound dressing to regulate chronic inflammation and provide an optimal environment for BM-MSCs to promote diabetic wound healing.https://doi.org/10.1177/2041731420947242
spellingShingle Haotian Bai
Noh Kyu-Cheol
Zhonghan Wang
Yutao Cui
He Liu
Hou Liu
Yubin Feng
Yue Zhao
Quan Lin
Zuhao Li
Regulation of inflammatory microenvironment using a self-healing hydrogel loaded with BM-MSCs for advanced wound healing in rat diabetic foot ulcers
Journal of Tissue Engineering
title Regulation of inflammatory microenvironment using a self-healing hydrogel loaded with BM-MSCs for advanced wound healing in rat diabetic foot ulcers
title_full Regulation of inflammatory microenvironment using a self-healing hydrogel loaded with BM-MSCs for advanced wound healing in rat diabetic foot ulcers
title_fullStr Regulation of inflammatory microenvironment using a self-healing hydrogel loaded with BM-MSCs for advanced wound healing in rat diabetic foot ulcers
title_full_unstemmed Regulation of inflammatory microenvironment using a self-healing hydrogel loaded with BM-MSCs for advanced wound healing in rat diabetic foot ulcers
title_short Regulation of inflammatory microenvironment using a self-healing hydrogel loaded with BM-MSCs for advanced wound healing in rat diabetic foot ulcers
title_sort regulation of inflammatory microenvironment using a self healing hydrogel loaded with bm mscs for advanced wound healing in rat diabetic foot ulcers
url https://doi.org/10.1177/2041731420947242
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