Dendronized chitosan hydrogel with GIT1 to accelerate bone defect repair through increasing local neovascular amount
Bone defects have long been a major healthcare issue because of the difficulties in regenerating bone mass volume and the high cost of treatment. G protein-coupled receptor kinase 2 interacting protein 1 (GIT1) has been proven to play an important role both in vascular development and in bone fractu...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | Bone Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352187223000608 |
| _version_ | 1797398577212817408 |
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| author | Lin Cheng Zhimin Zhou Qingqing Li Wen Li Xin Li Gen Li Jin Fan Lipeng Yu Guoyong Yin |
| author_facet | Lin Cheng Zhimin Zhou Qingqing Li Wen Li Xin Li Gen Li Jin Fan Lipeng Yu Guoyong Yin |
| author_sort | Lin Cheng |
| collection | DOAJ |
| description | Bone defects have long been a major healthcare issue because of the difficulties in regenerating bone mass volume and the high cost of treatment. G protein-coupled receptor kinase 2 interacting protein 1 (GIT1) has been proven to play an important role both in vascular development and in bone fracture healing. In this study, a type of thermoresponsive injectable hydrogel from oligoethylene glycol-based dendronized chitosan (G1-CS) was loaded with GIT1-plasmids (G1-CS/GIT1), and used to fill unicortical bone defects. RT-PCR analysis confirmed that G1-CS/GIT1 enhanced DNA transfection in MSCs both in vitro and in vivo. From the results of micro-CT, RT-PCR and histological analysis, it can be concluded that G1-CS/GIT1 accelerated the bone healing rate and increased the amount of neovascularization around the bone defects. In addition, an adeno-associated virus (AAV)-GIT1 was constructed to transfect mesenchymal stem cells. The results of capillary tube formation assay, immunofluorescence staining and western blot analysis proved that high expression of GIT1 induces mesenchymal stem cells to differentiate into endothelial cells. RT-PCR analysis and capillary tube formation assay confirmed that the Notch signaling pathway was activated in the differentiation process. Overall, we developed an efficient strategy through combination of injectable hydrogel and G1T1 for bone tissue engineering. |
| first_indexed | 2024-03-09T01:27:29Z |
| format | Article |
| id | doaj.art-9a97fbeb12104e7d808333f5f65b58f3 |
| institution | Directory Open Access Journal |
| issn | 2352-1872 |
| language | English |
| last_indexed | 2024-03-09T01:27:29Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Bone Reports |
| spelling | doaj.art-9a97fbeb12104e7d808333f5f65b58f32023-12-10T06:16:20ZengElsevierBone Reports2352-18722023-12-0119101712Dendronized chitosan hydrogel with GIT1 to accelerate bone defect repair through increasing local neovascular amountLin Cheng0Zhimin Zhou1Qingqing Li2Wen Li3Xin Li4Gen Li5Jin Fan6Lipeng Yu7Guoyong Yin8Department of Orthopedics, The Affiliated Hospital of Xuzhou Medical University, Huaihai West Road 99, Xuzhou, Jiangsu Province 221000, China; Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Guangzhou Road 300, Nanjing, Jiangsu Province 210000, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Guangzhou Road 300, Nanjing, Jiangsu Province 210000, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Guangzhou Road 300, Nanjing, Jiangsu Province 210000, ChinaSchool of Materials Science and Engineering, Shanghai University, Nanchen Street 333, Shanghai 200444, ChinaDepartment of Orthopedics, The Affiliated Hospital of Xuzhou Medical University, Huaihai West Road 99, Xuzhou, Jiangsu Province 221000, ChinaDepartment of Orthopedics, The Affiliated Hospital of Xuzhou Medical University, Huaihai West Road 99, Xuzhou, Jiangsu Province 221000, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Guangzhou Road 300, Nanjing, Jiangsu Province 210000, China; Corresponding authors.Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Guangzhou Road 300, Nanjing, Jiangsu Province 210000, China; Corresponding authors.Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Guangzhou Road 300, Nanjing, Jiangsu Province 210000, China; Corresponding authors.Bone defects have long been a major healthcare issue because of the difficulties in regenerating bone mass volume and the high cost of treatment. G protein-coupled receptor kinase 2 interacting protein 1 (GIT1) has been proven to play an important role both in vascular development and in bone fracture healing. In this study, a type of thermoresponsive injectable hydrogel from oligoethylene glycol-based dendronized chitosan (G1-CS) was loaded with GIT1-plasmids (G1-CS/GIT1), and used to fill unicortical bone defects. RT-PCR analysis confirmed that G1-CS/GIT1 enhanced DNA transfection in MSCs both in vitro and in vivo. From the results of micro-CT, RT-PCR and histological analysis, it can be concluded that G1-CS/GIT1 accelerated the bone healing rate and increased the amount of neovascularization around the bone defects. In addition, an adeno-associated virus (AAV)-GIT1 was constructed to transfect mesenchymal stem cells. The results of capillary tube formation assay, immunofluorescence staining and western blot analysis proved that high expression of GIT1 induces mesenchymal stem cells to differentiate into endothelial cells. RT-PCR analysis and capillary tube formation assay confirmed that the Notch signaling pathway was activated in the differentiation process. Overall, we developed an efficient strategy through combination of injectable hydrogel and G1T1 for bone tissue engineering.http://www.sciencedirect.com/science/article/pii/S2352187223000608Injectable hydrogelBone regenerationMesenchymal stem cellsGIT1Notch signaling |
| spellingShingle | Lin Cheng Zhimin Zhou Qingqing Li Wen Li Xin Li Gen Li Jin Fan Lipeng Yu Guoyong Yin Dendronized chitosan hydrogel with GIT1 to accelerate bone defect repair through increasing local neovascular amount Bone Reports Injectable hydrogel Bone regeneration Mesenchymal stem cells GIT1 Notch signaling |
| title | Dendronized chitosan hydrogel with GIT1 to accelerate bone defect repair through increasing local neovascular amount |
| title_full | Dendronized chitosan hydrogel with GIT1 to accelerate bone defect repair through increasing local neovascular amount |
| title_fullStr | Dendronized chitosan hydrogel with GIT1 to accelerate bone defect repair through increasing local neovascular amount |
| title_full_unstemmed | Dendronized chitosan hydrogel with GIT1 to accelerate bone defect repair through increasing local neovascular amount |
| title_short | Dendronized chitosan hydrogel with GIT1 to accelerate bone defect repair through increasing local neovascular amount |
| title_sort | dendronized chitosan hydrogel with git1 to accelerate bone defect repair through increasing local neovascular amount |
| topic | Injectable hydrogel Bone regeneration Mesenchymal stem cells GIT1 Notch signaling |
| url | http://www.sciencedirect.com/science/article/pii/S2352187223000608 |
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