Low-Molecular-Weight Heparin-Functionalized Chitosan-Chondroitin Sulfate Hydrogels for Controlled Release of TGF-β3 and in vitro Neocartilage Formation
Repair of hyaline cartilage remains a huge challenge in clinic because of the avascular and aneural characteristics and the paucity of endogenous repair cells. Recently, tissue engineering technique, possessing unique capacity of repairing large tissue defects, avoiding donor complications and two-s...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-11-01
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| Series: | Frontiers in Chemistry |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fchem.2019.00745/full |
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| author | You-Rong Chen Zhu-Xing Zhou Ji-Ying Zhang Fu-Zhen Yuan Bing-Bing Xu Jian Guan Chao Han Chao Han Dong Jiang Yan-Yu Yang Yan-Yu Yang Jia-Kuo Yu |
| author_facet | You-Rong Chen Zhu-Xing Zhou Ji-Ying Zhang Fu-Zhen Yuan Bing-Bing Xu Jian Guan Chao Han Chao Han Dong Jiang Yan-Yu Yang Yan-Yu Yang Jia-Kuo Yu |
| author_sort | You-Rong Chen |
| collection | DOAJ |
| description | Repair of hyaline cartilage remains a huge challenge in clinic because of the avascular and aneural characteristics and the paucity of endogenous repair cells. Recently, tissue engineering technique, possessing unique capacity of repairing large tissue defects, avoiding donor complications and two-stage invasive surgical procedures, has been developed a promising therapeutic strategy for cartilage injury. In this study, we incorporated low-molecular-weight heparin (LMWH) into carboxymethyl chitosan-oxidized chondroitin sulfate (CMC-OCS) hydrogel for loading transforming growth factor-β3 (TGF-β3) as matrix of peripheral blood mesenchymal stem cells (PB-MSCs) to construct tissue-engineered cartilage. Meanwhile, three control hydrogels with or without LMWH and/or TGF-β3 were also prepared. The gelling time, microstructures, mechanical properties, degradation rate, cytotoxicity, and the release of TGF-β3 of different hydrogels were investigated. In vitro experiments evaluated the tri-lineage differentiation potential of PB-MSCs, combined with the proliferation, distribution, viability, morphology, and chondrogenic differentiation. Compared with non-LMWH-hydrogels, LMWH-hydrogels (LMWH-CMC-OCS-TGF-β3) have shorter gelling time, higher mechanical strength, slower degradation rate and more stable and lasting release of TGF-β3. After two weeks of culture in vitro, expression of cartilage-specific genes collagen type-2 (COL-2) and aggrecan (AGC), and secretion of glycosaminoglycan (GAG), and COL-2 proteins in LMWH-CMC-OCS-TGF-β3 group were significantly higher than those in other groups. COL-2 immunofluorescence staining showed that the proportion of COL-2 positive cells and immunofluorescence intensity in LMWH-CMC-OCS-TGF-β3 hydrogel were significantly higher than those in other groups. The LMWH-CMC-OCS-TGF-β3 hydrogel can slowly release TGF-β3 in a long term, and meanwhile the hydrogel can provide a biocompatible microenvironment for the growth and chondrogenic differentiation of PB-MSCs. Thus, LMWH functionalized CMC-OCS hydrogels proposed in this work will be beneficial for constructing functional scaffolds for tissue-engineered cartilage. |
| first_indexed | 2024-12-21T16:13:16Z |
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| id | doaj.art-a3d3e5025c974faf9ade9297c27b0738 |
| institution | Directory Open Access Journal |
| issn | 2296-2646 |
| language | English |
| last_indexed | 2024-12-21T16:13:16Z |
| publishDate | 2019-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Chemistry |
| spelling | doaj.art-a3d3e5025c974faf9ade9297c27b07382022-12-21T18:57:46ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462019-11-01710.3389/fchem.2019.00745492325Low-Molecular-Weight Heparin-Functionalized Chitosan-Chondroitin Sulfate Hydrogels for Controlled Release of TGF-β3 and in vitro Neocartilage FormationYou-Rong Chen0Zhu-Xing Zhou1Ji-Ying Zhang2Fu-Zhen Yuan3Bing-Bing Xu4Jian Guan5Chao Han6Chao Han7Dong Jiang8Yan-Yu Yang9Yan-Yu Yang10Jia-Kuo Yu11Knee Surgery Department of the Institute of Sports Medicine, Peking University Third Hospital, Beijing, ChinaKnee Surgery Department of the Institute of Sports Medicine, Peking University Third Hospital, Beijing, ChinaKnee Surgery Department of the Institute of Sports Medicine, Peking University Third Hospital, Beijing, ChinaKnee Surgery Department of the Institute of Sports Medicine, Peking University Third Hospital, Beijing, ChinaKnee Surgery Department of the Institute of Sports Medicine, Peking University Third Hospital, Beijing, ChinaKnee Surgery Department of the Institute of Sports Medicine, Peking University Third Hospital, Beijing, ChinaKnee Surgery Department of the Institute of Sports Medicine, Peking University Third Hospital, Beijing, ChinaSchool of Clinical Medicine, Weifang Medical University, Weifang, ChinaKnee Surgery Department of the Institute of Sports Medicine, Peking University Third Hospital, Beijing, ChinaBeijing National Laboratory for Molecular Sciences, State Key Laboratory of Polymer Physics & Chemistry, Institute of Chemistry, Chinese Academy of Sciences, Beijing, ChinaCollege of Materials Science and Engineering, Zhengzhou University, Zhengzhou, ChinaKnee Surgery Department of the Institute of Sports Medicine, Peking University Third Hospital, Beijing, ChinaRepair of hyaline cartilage remains a huge challenge in clinic because of the avascular and aneural characteristics and the paucity of endogenous repair cells. Recently, tissue engineering technique, possessing unique capacity of repairing large tissue defects, avoiding donor complications and two-stage invasive surgical procedures, has been developed a promising therapeutic strategy for cartilage injury. In this study, we incorporated low-molecular-weight heparin (LMWH) into carboxymethyl chitosan-oxidized chondroitin sulfate (CMC-OCS) hydrogel for loading transforming growth factor-β3 (TGF-β3) as matrix of peripheral blood mesenchymal stem cells (PB-MSCs) to construct tissue-engineered cartilage. Meanwhile, three control hydrogels with or without LMWH and/or TGF-β3 were also prepared. The gelling time, microstructures, mechanical properties, degradation rate, cytotoxicity, and the release of TGF-β3 of different hydrogels were investigated. In vitro experiments evaluated the tri-lineage differentiation potential of PB-MSCs, combined with the proliferation, distribution, viability, morphology, and chondrogenic differentiation. Compared with non-LMWH-hydrogels, LMWH-hydrogels (LMWH-CMC-OCS-TGF-β3) have shorter gelling time, higher mechanical strength, slower degradation rate and more stable and lasting release of TGF-β3. After two weeks of culture in vitro, expression of cartilage-specific genes collagen type-2 (COL-2) and aggrecan (AGC), and secretion of glycosaminoglycan (GAG), and COL-2 proteins in LMWH-CMC-OCS-TGF-β3 group were significantly higher than those in other groups. COL-2 immunofluorescence staining showed that the proportion of COL-2 positive cells and immunofluorescence intensity in LMWH-CMC-OCS-TGF-β3 hydrogel were significantly higher than those in other groups. The LMWH-CMC-OCS-TGF-β3 hydrogel can slowly release TGF-β3 in a long term, and meanwhile the hydrogel can provide a biocompatible microenvironment for the growth and chondrogenic differentiation of PB-MSCs. Thus, LMWH functionalized CMC-OCS hydrogels proposed in this work will be beneficial for constructing functional scaffolds for tissue-engineered cartilage.https://www.frontiersin.org/article/10.3389/fchem.2019.00745/fulllow-molecular-weight heparinhydrogelcontrolled releaseperipheral blood mesenchymal stem celltissue-engineered cartilage |
| spellingShingle | You-Rong Chen Zhu-Xing Zhou Ji-Ying Zhang Fu-Zhen Yuan Bing-Bing Xu Jian Guan Chao Han Chao Han Dong Jiang Yan-Yu Yang Yan-Yu Yang Jia-Kuo Yu Low-Molecular-Weight Heparin-Functionalized Chitosan-Chondroitin Sulfate Hydrogels for Controlled Release of TGF-β3 and in vitro Neocartilage Formation Frontiers in Chemistry low-molecular-weight heparin hydrogel controlled release peripheral blood mesenchymal stem cell tissue-engineered cartilage |
| title | Low-Molecular-Weight Heparin-Functionalized Chitosan-Chondroitin Sulfate Hydrogels for Controlled Release of TGF-β3 and in vitro Neocartilage Formation |
| title_full | Low-Molecular-Weight Heparin-Functionalized Chitosan-Chondroitin Sulfate Hydrogels for Controlled Release of TGF-β3 and in vitro Neocartilage Formation |
| title_fullStr | Low-Molecular-Weight Heparin-Functionalized Chitosan-Chondroitin Sulfate Hydrogels for Controlled Release of TGF-β3 and in vitro Neocartilage Formation |
| title_full_unstemmed | Low-Molecular-Weight Heparin-Functionalized Chitosan-Chondroitin Sulfate Hydrogels for Controlled Release of TGF-β3 and in vitro Neocartilage Formation |
| title_short | Low-Molecular-Weight Heparin-Functionalized Chitosan-Chondroitin Sulfate Hydrogels for Controlled Release of TGF-β3 and in vitro Neocartilage Formation |
| title_sort | low molecular weight heparin functionalized chitosan chondroitin sulfate hydrogels for controlled release of tgf β3 and in vitro neocartilage formation |
| topic | low-molecular-weight heparin hydrogel controlled release peripheral blood mesenchymal stem cell tissue-engineered cartilage |
| url | https://www.frontiersin.org/article/10.3389/fchem.2019.00745/full |
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