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

被引:57
作者
Chen, You-Rong [1 ,2 ]
Yan, Xin [1 ,2 ]
Yuan, Fu-Zhen [1 ,2 ]
Lin, Lin [1 ,2 ]
Wang, Shao-Jie [3 ]
Ye, Jing [1 ,2 ]
Zhang, Ji-Ying [1 ,2 ]
Yang, Meng [1 ,2 ]
Wu, De-Cheng [4 ]
Wang, Xing [5 ]
Yu, Jia-Kuo [1 ,2 ]
机构
[1] Peking Univ Third Hosp, Beijing Key Lab Sports Injuries, Dept Sports Med, Beijing 100191, Peoples R China
[2] Peking Univ, Inst Sports Med, Beijing 100191, Peoples R China
[3] Xiamen Univ, Dept Joint Surg & Sports Med, Zhongshan Hosp, Xiamen 361000, Peoples R China
[4] Southern Univ Sci & Technol, Dept Biomed Engn, Shenzhen 518055, Peoples R China
[5] Chinese Acad Sci, Inst Chem, State Key Lab Polymer Phys & Chem, Beijing Natl Lab Mol Sci, Beijing 100190, Peoples R China
基金
中国国家自然科学基金;
关键词
cartilage regeneration; cell tracing; double-network hydrogels; kartogenin; mesenchymal stem cells; IN-VITRO; COMPOSITE HYDROGELS; ARTICULAR-CARTILAGE; PERIPHERAL-BLOOD; GROWTH-FACTOR; BONE-MARROW; REGENERATION; DELIVERY; SCAFFOLD;
D O I
10.1002/advs.202105571
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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.
引用
收藏
页数:13
相关论文
共 50 条
[1]   Bioinspired Ultratough Hydrogel with Fast Recovery, Self-Healing, Injectability and Cytocompatibility [J].
Azevedo, Sara ;
Costa, Ana M. S. ;
Andersen, Amanda ;
Choi, Insung S. ;
Birkedal, Henrik ;
Mono, Joao F. .
ADVANCED MATERIALS, 2017, 29 (28)
[2]  
Bai Haijing, 2019, Biomed Res Int, V2019, P8597953, DOI 10.1155/2019/8597953
[3]   The Use of Peripheral Blood-Derived Stem Cells for Cartilage Repair and Regeneration In Vivo: A Review [J].
Chen, You-Rong ;
Yan, Xin ;
Yuan, Fu-Zhen ;
Ye, Jing ;
Xu, Bing-Bing ;
Zhou, Zhu-Xing ;
Mao, Zi-Mu ;
Guan, Jian ;
Song, Yi-Fan ;
Sun, Ze-Wen ;
Wang, Xin-Jie ;
Chen, Ze-Yi ;
Wang, Ding-Yu ;
Fan, Bao-Shi ;
Yang, Meng ;
Song, Shi-Tang ;
Jiang, Dong ;
Yu, Jia-Kuo .
FRONTIERS IN PHARMACOLOGY, 2020, 11
[4]   Low-Molecular-Weight Heparin-Functionalized Chitosan-Chondroitin Sulfate Hydrogels for Controlled Release of TGF-β3 and in vitro Neocartilage Formation [J].
Chen, You-Rong ;
Zhou, Zhu-Xing ;
Zhang, Ji-Ying ;
Yuan, Fu-Zhen ;
Xu, Bing-Bing ;
Guan, Jian ;
Han, Chao ;
Jiang, Dong ;
Yang, Yan-Yu ;
Yu, Jia-Kuo .
FRONTIERS IN CHEMISTRY, 2019, 7
[5]   DNA-Grafted Hyaluronic Acid System with Enhanced Injectability and Biostability for Photo-Controlled Osteoarthritis Gene Therapy [J].
Chen, Zhijie ;
Zhang, Feng ;
Zhang, Hongbo ;
Cheng, Liang ;
Chen, Kaizhe ;
Shen, Jieliang ;
Qi, Jin ;
Deng, Lianfu ;
He, Chuan ;
Santos, Helder A. ;
Cui, Wenguo .
ADVANCED SCIENCE, 2021, 8 (09)
[6]   Dual delivery of stem cells and insulin-like growth factor-1 in coacervate-embedded composite hydrogels for enhanced cartilage regeneration in osteochondral defects [J].
Cho, Hyeran ;
Kim, Junhyung ;
Kim, Sungjun ;
Jung, Yun Chan ;
Wang, Yadong ;
Kang, Byung-Jae ;
Kim, Kyobum .
JOURNAL OF CONTROLLED RELEASE, 2020, 327 :284-295
[7]   Cyclin B2 is required for progression through meiosis in mouse oocytes [J].
Daldello, Enrico Maria ;
Luong, Xuan G. ;
Yang, Cai-Rong ;
Kuhn, Jonathan ;
Conti, Marco .
DEVELOPMENT, 2019, 146 (08)
[8]   Cost-efficacy of Knee Cartilage Defect Treatments in the United States [J].
Everhart, Joshua S. ;
Campbell, Andrew B. ;
Abouljoud, Moneer M. ;
Kirven, J. Caid ;
Flanigan, David C. .
AMERICAN JOURNAL OF SPORTS MEDICINE, 2020, 48 (01) :242-251
[9]   Principles for establishment of the stem cell bank and its applications on management of sports injuries [J].
Fan, Bao-Shi ;
Liu, Yang ;
Zhang, Ji-Ying ;
Chen, You-Rong ;
Yang, Meng ;
Yu, Jia-Kuo .
STEM CELL RESEARCH & THERAPY, 2021, 12 (01)
[10]   A New Source of Mesenchymal Stem Cells for Articular Cartilage Repair MSCs Derived From Mobilized Peripheral Blood Share Similar Biological Characteristics In Vitro and Chondrogenesis In Vivo as MSCs From Bone Marrow in a Rabbit Model [J].
Fu, Wei-Li ;
Zhou, Chun-Yan ;
Yu, Jia-Kuo .
AMERICAN JOURNAL OF SPORTS MEDICINE, 2014, 42 (03) :592-601