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Cartilage repair mediated by thermosensitive photocrosslinkable TGFβ1-loaded GM-HPCH via immunomodulating macrophages, recruiting MSCs and promoting chondrogenesis

Repairing cartilage defects using thermosensitive hydrogels is an attractive treatment strategy, but the poor mechanical properties and limited understanding of the interactions between hydrogels and cells limit their application. Methods: In this study, a thermosensitive hydroxypropyl chitin hydrog...

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Autores principales: Ji, Xiongfa, Lei, Zehua, Yuan, Meng, Zhu, Hao, Yuan, Xi, Liu, Wenbin, Pu, Hongxu, Jiang, Jiawei, Zhang, Yu, Jiang, Xulin, Xiao, Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052899/
https://www.ncbi.nlm.nih.gov/pubmed/32194841
http://dx.doi.org/10.7150/thno.41622
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author Ji, Xiongfa
Lei, Zehua
Yuan, Meng
Zhu, Hao
Yuan, Xi
Liu, Wenbin
Pu, Hongxu
Jiang, Jiawei
Zhang, Yu
Jiang, Xulin
Xiao, Jun
author_facet Ji, Xiongfa
Lei, Zehua
Yuan, Meng
Zhu, Hao
Yuan, Xi
Liu, Wenbin
Pu, Hongxu
Jiang, Jiawei
Zhang, Yu
Jiang, Xulin
Xiao, Jun
author_sort Ji, Xiongfa
collection PubMed
description Repairing cartilage defects using thermosensitive hydrogels is an attractive treatment strategy, but the poor mechanical properties and limited understanding of the interactions between hydrogels and cells limit their application. Methods: In this study, a thermosensitive hydroxypropyl chitin hydrogel (HPCH) was functionalized with methacrylate groups to synthesize photocrosslinkable glycidyl methacrylate-modified HPCH (GM-HPCH). GM-HPCH could form a gel in situ through a thermosensitive sol-gel transition and its mechanical properties can be improved by UV irradiation. Cell viability, cell adhesion and anti-apoptosis activity of GM-HPCH were evaluated. Transforming growth factor-β1 (TGFβ1) was introduced into the GM-HPCH hydrogel to fabricate the composite hydrogel. The macrophage immunomodulation, MSC recruitment and chondrogenesis of the composite hydrogel were evaluated. Results: With high biocompatibility, GM-HPCH could protect chondrocytes from apoptosis. Both the in vitro and in vivo experiments showed that GM-HPCH + TGFβ1 shifted the recruited macrophages from M1 to M2 and promoted chondrogenic gene expression. Additionally, the composite hydrogel could promote the migration of marrow stromal cells (MSCs) in the Transwell test and increase migrated gene expression. The fluorescent tracking of MSCs confirmed MSC homing in the rat chondral defect with the help of GM-HPCH. The macroscopic evaluation and histological results at 6 weeks and 12 weeks postsurgery showed that GM-HPCH + TGFβ1 can achieve superior cartilage healing. Conclusions: The GM-HPCH + TGFβ1 hydrogel effectively promoted cartilage repair via immunomodulating macrophages, recruiting MSCs and promoting chondrogenesis; thus it is a promising injectable hydrogel for cartilage regeneration.
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spelling pubmed-70528992020-03-19 Cartilage repair mediated by thermosensitive photocrosslinkable TGFβ1-loaded GM-HPCH via immunomodulating macrophages, recruiting MSCs and promoting chondrogenesis Ji, Xiongfa Lei, Zehua Yuan, Meng Zhu, Hao Yuan, Xi Liu, Wenbin Pu, Hongxu Jiang, Jiawei Zhang, Yu Jiang, Xulin Xiao, Jun Theranostics Research Paper Repairing cartilage defects using thermosensitive hydrogels is an attractive treatment strategy, but the poor mechanical properties and limited understanding of the interactions between hydrogels and cells limit their application. Methods: In this study, a thermosensitive hydroxypropyl chitin hydrogel (HPCH) was functionalized with methacrylate groups to synthesize photocrosslinkable glycidyl methacrylate-modified HPCH (GM-HPCH). GM-HPCH could form a gel in situ through a thermosensitive sol-gel transition and its mechanical properties can be improved by UV irradiation. Cell viability, cell adhesion and anti-apoptosis activity of GM-HPCH were evaluated. Transforming growth factor-β1 (TGFβ1) was introduced into the GM-HPCH hydrogel to fabricate the composite hydrogel. The macrophage immunomodulation, MSC recruitment and chondrogenesis of the composite hydrogel were evaluated. Results: With high biocompatibility, GM-HPCH could protect chondrocytes from apoptosis. Both the in vitro and in vivo experiments showed that GM-HPCH + TGFβ1 shifted the recruited macrophages from M1 to M2 and promoted chondrogenic gene expression. Additionally, the composite hydrogel could promote the migration of marrow stromal cells (MSCs) in the Transwell test and increase migrated gene expression. The fluorescent tracking of MSCs confirmed MSC homing in the rat chondral defect with the help of GM-HPCH. The macroscopic evaluation and histological results at 6 weeks and 12 weeks postsurgery showed that GM-HPCH + TGFβ1 can achieve superior cartilage healing. Conclusions: The GM-HPCH + TGFβ1 hydrogel effectively promoted cartilage repair via immunomodulating macrophages, recruiting MSCs and promoting chondrogenesis; thus it is a promising injectable hydrogel for cartilage regeneration. Ivyspring International Publisher 2020-02-03 /pmc/articles/PMC7052899/ /pubmed/32194841 http://dx.doi.org/10.7150/thno.41622 Text en © The author(s) This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Ji, Xiongfa
Lei, Zehua
Yuan, Meng
Zhu, Hao
Yuan, Xi
Liu, Wenbin
Pu, Hongxu
Jiang, Jiawei
Zhang, Yu
Jiang, Xulin
Xiao, Jun
Cartilage repair mediated by thermosensitive photocrosslinkable TGFβ1-loaded GM-HPCH via immunomodulating macrophages, recruiting MSCs and promoting chondrogenesis
title Cartilage repair mediated by thermosensitive photocrosslinkable TGFβ1-loaded GM-HPCH via immunomodulating macrophages, recruiting MSCs and promoting chondrogenesis
title_full Cartilage repair mediated by thermosensitive photocrosslinkable TGFβ1-loaded GM-HPCH via immunomodulating macrophages, recruiting MSCs and promoting chondrogenesis
title_fullStr Cartilage repair mediated by thermosensitive photocrosslinkable TGFβ1-loaded GM-HPCH via immunomodulating macrophages, recruiting MSCs and promoting chondrogenesis
title_full_unstemmed Cartilage repair mediated by thermosensitive photocrosslinkable TGFβ1-loaded GM-HPCH via immunomodulating macrophages, recruiting MSCs and promoting chondrogenesis
title_short Cartilage repair mediated by thermosensitive photocrosslinkable TGFβ1-loaded GM-HPCH via immunomodulating macrophages, recruiting MSCs and promoting chondrogenesis
title_sort cartilage repair mediated by thermosensitive photocrosslinkable tgfβ1-loaded gm-hpch via immunomodulating macrophages, recruiting mscs and promoting chondrogenesis
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052899/
https://www.ncbi.nlm.nih.gov/pubmed/32194841
http://dx.doi.org/10.7150/thno.41622
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