Kartogenin‐Conjugated Double‐Network Hydrogel Combined with Stem Cell Transplantation and Tracing for Cartilage Repair

Abstract The effectiveness of existing tissue‐engineering cartilage (TEC) is known to be hampered by weak integration of biocompatibility, biodegradation, mechanical strength, and microenvironment supplies. The strategy of hydrogel‐based TEC holds considerable promise in circumventing these problems...

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Main Authors: You‐Rong Chen, Xin Yan, Fu‐Zhen Yuan, Lin Lin, Shao‐Jie Wang, Jing Ye, Ji‐Ying Zhang, Meng Yang, De‐Cheng Wu, Xing Wang, Jia‐Kuo Yu
Format: Article
Language:English
Published: Wiley 2022-12-01
Series:Advanced Science
Subjects:
Online Access:https://doi.org/10.1002/advs.202105571
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author You‐Rong Chen
Xin Yan
Fu‐Zhen Yuan
Lin Lin
Shao‐Jie Wang
Jing Ye
Ji‐Ying Zhang
Meng Yang
De‐Cheng Wu
Xing Wang
Jia‐Kuo Yu
author_facet You‐Rong Chen
Xin Yan
Fu‐Zhen Yuan
Lin Lin
Shao‐Jie Wang
Jing Ye
Ji‐Ying Zhang
Meng Yang
De‐Cheng Wu
Xing Wang
Jia‐Kuo Yu
author_sort You‐Rong Chen
collection DOAJ
description Abstract The effectiveness of existing tissue‐engineering cartilage (TEC) is known to be hampered by weak integration of biocompatibility, biodegradation, mechanical strength, and microenvironment supplies. The strategy of hydrogel‐based TEC holds considerable promise in circumventing these problems. Herein, a non‐toxic, biodegradable, and mechanically optimized double‐network (DN) hydrogel consisting of polyethylene glycol (PEG) and kartogenin (KGN)‐conjugated chitosan (CHI) is constructed using a simple soaking strategy. This PEG‐CHI‐KGN DN hydrogel possesses favorable architectures, suitable mechanics, remarkable cellular affinity, and sustained KGN release, which can facilitate the cartilage‐specific genes expression and extracellular matrix secretion of peripheral blood‐derived mesenchymal stem cells (PB‐MSCs). Notably, after tracing the transplanted cells by detecting the rabbit sex‐determining region Y‐linked gene sequence, the allogeneic PB‐MSCs are found to survive for even 3 months in the regenerated cartilage. Here, the long‐term release of KGN is able to efficiently and persistently activate multiple genes and signaling pathways to promote the chondrogenesis, chondrocyte differentiation, and survival of PB‐MSCs. Thus, the regenerated tissues exhibit well‐matched histomorphology and biomechanical performance such as native cartilage. Consequently, it is believed this innovative work can expand the choice for developing the next generation of orthopedic implants in the loadbearing region of a living body.
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spelling doaj.art-82c1188286a74913a181e8a7b53f161f2022-12-22T03:53:46ZengWileyAdvanced Science2198-38442022-12-01935n/an/a10.1002/advs.202105571Kartogenin‐Conjugated Double‐Network Hydrogel Combined with Stem Cell Transplantation and Tracing for Cartilage RepairYou‐Rong Chen0Xin Yan1Fu‐Zhen Yuan2Lin Lin3Shao‐Jie Wang4Jing Ye5Ji‐Ying Zhang6Meng Yang7De‐Cheng Wu8Xing Wang9Jia‐Kuo Yu10Department of Sports Medicine Beijing Key Laboratory of Sports Injuries Peking University Third Hospital Beijing 100191 ChinaDepartment of Sports Medicine Beijing Key Laboratory of Sports Injuries Peking University Third Hospital Beijing 100191 ChinaDepartment of Sports Medicine Beijing Key Laboratory of Sports Injuries Peking University Third Hospital Beijing 100191 ChinaDepartment of Sports Medicine Beijing Key Laboratory of Sports Injuries Peking University Third Hospital Beijing 100191 ChinaDepartment of Joint Surgery and Sports Medicine, Zhongshan Hospital Xiamen University Xiamen 361000 ChinaDepartment of Sports Medicine Beijing Key Laboratory of Sports Injuries Peking University Third Hospital Beijing 100191 ChinaDepartment of Sports Medicine Beijing Key Laboratory of Sports Injuries Peking University Third Hospital Beijing 100191 ChinaDepartment of Sports Medicine Beijing Key Laboratory of Sports Injuries Peking University Third Hospital Beijing 100191 ChinaDepartment of Biomedical Engineering Southern University of Science and Technology Shenzhen 518055 ChinaBeijing National Laboratory for Molecular Sciences State Key Laboratory of Polymer Physics and Chemistry Institute of Chemistry Chinese Academy of Sciences Beijing 100190 ChinaDepartment of Sports Medicine Beijing Key Laboratory of Sports Injuries Peking University Third Hospital Beijing 100191 ChinaAbstract The effectiveness of existing tissue‐engineering cartilage (TEC) is known to be hampered by weak integration of biocompatibility, biodegradation, mechanical strength, and microenvironment supplies. The strategy of hydrogel‐based TEC holds considerable promise in circumventing these problems. Herein, a non‐toxic, biodegradable, and mechanically optimized double‐network (DN) hydrogel consisting of polyethylene glycol (PEG) and kartogenin (KGN)‐conjugated chitosan (CHI) is constructed using a simple soaking strategy. This PEG‐CHI‐KGN DN hydrogel possesses favorable architectures, suitable mechanics, remarkable cellular affinity, and sustained KGN release, which can facilitate the cartilage‐specific genes expression and extracellular matrix secretion of peripheral blood‐derived mesenchymal stem cells (PB‐MSCs). Notably, after tracing the transplanted cells by detecting the rabbit sex‐determining region Y‐linked gene sequence, the allogeneic PB‐MSCs are found to survive for even 3 months in the regenerated cartilage. Here, the long‐term release of KGN is able to efficiently and persistently activate multiple genes and signaling pathways to promote the chondrogenesis, chondrocyte differentiation, and survival of PB‐MSCs. Thus, the regenerated tissues exhibit well‐matched histomorphology and biomechanical performance such as native cartilage. Consequently, it is believed this innovative work can expand the choice for developing the next generation of orthopedic implants in the loadbearing region of a living body.https://doi.org/10.1002/advs.202105571cartilage regenerationcell tracingdouble‐network hydrogelskartogeninmesenchymal stem cells
spellingShingle You‐Rong Chen
Xin Yan
Fu‐Zhen Yuan
Lin Lin
Shao‐Jie Wang
Jing Ye
Ji‐Ying Zhang
Meng Yang
De‐Cheng Wu
Xing Wang
Jia‐Kuo Yu
Kartogenin‐Conjugated Double‐Network Hydrogel Combined with Stem Cell Transplantation and Tracing for Cartilage Repair
Advanced Science
cartilage regeneration
cell tracing
double‐network hydrogels
kartogenin
mesenchymal stem cells
title Kartogenin‐Conjugated Double‐Network Hydrogel Combined with Stem Cell Transplantation and Tracing for Cartilage Repair
title_full Kartogenin‐Conjugated Double‐Network Hydrogel Combined with Stem Cell Transplantation and Tracing for Cartilage Repair
title_fullStr Kartogenin‐Conjugated Double‐Network Hydrogel Combined with Stem Cell Transplantation and Tracing for Cartilage Repair
title_full_unstemmed Kartogenin‐Conjugated Double‐Network Hydrogel Combined with Stem Cell Transplantation and Tracing for Cartilage Repair
title_short Kartogenin‐Conjugated Double‐Network Hydrogel Combined with Stem Cell Transplantation and Tracing for Cartilage Repair
title_sort kartogenin conjugated double network hydrogel combined with stem cell transplantation and tracing for cartilage repair
topic cartilage regeneration
cell tracing
double‐network hydrogels
kartogenin
mesenchymal stem cells
url https://doi.org/10.1002/advs.202105571
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