Genipin Cross-Linked Decellularized Nucleus Pulposus Hydrogel-Like Cell Delivery System Induces Differentiation of ADSCs and Retards Intervertebral Disc Degeneration
Intervertebral disc degeneration (IDD) is the pathological basis of disc degenerative diseases (DDD). Reduction in the number of cells and degeneration of the extracellular matrix (ECM) in the nucleus pulposus (NP) are characteristics of IDD. Bio-hydrogel combined with stem cell transplantation is a...
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Frontiers Media S.A.
2021-12-01
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| Series: | Frontiers in Bioengineering and Biotechnology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fbioe.2021.807883/full |
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| author | Lei Yu Yi Liu Jianxin Wu Shuang Wang Jiangming Yu Weiheng Wang Xiaojian Ye |
| author_facet | Lei Yu Yi Liu Jianxin Wu Shuang Wang Jiangming Yu Weiheng Wang Xiaojian Ye |
| author_sort | Lei Yu |
| collection | DOAJ |
| description | Intervertebral disc degeneration (IDD) is the pathological basis of disc degenerative diseases (DDD). Reduction in the number of cells and degeneration of the extracellular matrix (ECM) in the nucleus pulposus (NP) are characteristics of IDD. Bio-hydrogel combined with stem cell transplantation is a promising treatment. Injectable ECM hydrogels have good biological activity and in-situ gelatinization. However, its biomechanics and stability are insufficient to provide adequate mechanical support for intervertebral discs and to maintain the long-term differential stimulus for seeded stem cells. In our study, we developed genipin cross-linked decellularized nucleus pulposus hydrogel (GDH) as delivery system. We evaluated the mechanical properties, stability, biocompatibility, and differentiation induction of GDH cross-linked with different concentrations of genipin in vitro. The GDH-loaded adipose-derived mesenchymal stem cells (ADSCs) (GDHA) were injected into the rat degenerated coccygeal intervertebral disc. The effect of intervertebral disc regeneration in vivo was evaluated. The results showed that GDH with 0.02% of genipin had similar elastic modulus to human nucleus pulposus, good biocompatibility, and inducibility of expressing NP-related genes. In vivo studies showed that GDHA improved the survival of ADSCs and improved the intervertebral height, MRI index, and histological grading score. In conclusion, GDH, as an outstanding bio-hydrogel cell delivery system, has the therapeutic potential for retarding IDD. |
| first_indexed | 2024-12-20T14:57:12Z |
| format | Article |
| id | doaj.art-7450dd096762497c8754335630778bca |
| institution | Directory Open Access Journal |
| issn | 2296-4185 |
| language | English |
| last_indexed | 2024-12-20T14:57:12Z |
| publishDate | 2021-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Bioengineering and Biotechnology |
| spelling | doaj.art-7450dd096762497c8754335630778bca2022-12-21T19:36:46ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852021-12-01910.3389/fbioe.2021.807883807883Genipin Cross-Linked Decellularized Nucleus Pulposus Hydrogel-Like Cell Delivery System Induces Differentiation of ADSCs and Retards Intervertebral Disc DegenerationLei Yu0Yi Liu1Jianxin Wu2Shuang Wang3Jiangming Yu4Weiheng Wang5Xiaojian Ye6Department of Orthopedics, Second Affiliated Hospital of Naval Medical University, Shanghai, ChinaDepartment of Orthopedics, Second Affiliated Hospital of Naval Medical University, Shanghai, ChinaDepartment of Orthopedics, First Affiliated Hospital of Naval Medical University, Shanghai, ChinaDepartment of Orthopedics, Second Affiliated Hospital of Naval Medical University, Shanghai, ChinaDepartment of Orthopaedics, Tongren Hospital, Shanghai Jiaotong University, Shanghai, ChinaDepartment of Orthopedics, Second Affiliated Hospital of Naval Medical University, Shanghai, ChinaDepartment of Orthopaedics, Tongren Hospital, Shanghai Jiaotong University, Shanghai, ChinaIntervertebral disc degeneration (IDD) is the pathological basis of disc degenerative diseases (DDD). Reduction in the number of cells and degeneration of the extracellular matrix (ECM) in the nucleus pulposus (NP) are characteristics of IDD. Bio-hydrogel combined with stem cell transplantation is a promising treatment. Injectable ECM hydrogels have good biological activity and in-situ gelatinization. However, its biomechanics and stability are insufficient to provide adequate mechanical support for intervertebral discs and to maintain the long-term differential stimulus for seeded stem cells. In our study, we developed genipin cross-linked decellularized nucleus pulposus hydrogel (GDH) as delivery system. We evaluated the mechanical properties, stability, biocompatibility, and differentiation induction of GDH cross-linked with different concentrations of genipin in vitro. The GDH-loaded adipose-derived mesenchymal stem cells (ADSCs) (GDHA) were injected into the rat degenerated coccygeal intervertebral disc. The effect of intervertebral disc regeneration in vivo was evaluated. The results showed that GDH with 0.02% of genipin had similar elastic modulus to human nucleus pulposus, good biocompatibility, and inducibility of expressing NP-related genes. In vivo studies showed that GDHA improved the survival of ADSCs and improved the intervertebral height, MRI index, and histological grading score. In conclusion, GDH, as an outstanding bio-hydrogel cell delivery system, has the therapeutic potential for retarding IDD.https://www.frontiersin.org/articles/10.3389/fbioe.2021.807883/fullintervertebral disc degenerationgenipinnucleus pulposusADSCtissue engineering |
| spellingShingle | Lei Yu Yi Liu Jianxin Wu Shuang Wang Jiangming Yu Weiheng Wang Xiaojian Ye Genipin Cross-Linked Decellularized Nucleus Pulposus Hydrogel-Like Cell Delivery System Induces Differentiation of ADSCs and Retards Intervertebral Disc Degeneration Frontiers in Bioengineering and Biotechnology intervertebral disc degeneration genipin nucleus pulposus ADSC tissue engineering |
| title | Genipin Cross-Linked Decellularized Nucleus Pulposus Hydrogel-Like Cell Delivery System Induces Differentiation of ADSCs and Retards Intervertebral Disc Degeneration |
| title_full | Genipin Cross-Linked Decellularized Nucleus Pulposus Hydrogel-Like Cell Delivery System Induces Differentiation of ADSCs and Retards Intervertebral Disc Degeneration |
| title_fullStr | Genipin Cross-Linked Decellularized Nucleus Pulposus Hydrogel-Like Cell Delivery System Induces Differentiation of ADSCs and Retards Intervertebral Disc Degeneration |
| title_full_unstemmed | Genipin Cross-Linked Decellularized Nucleus Pulposus Hydrogel-Like Cell Delivery System Induces Differentiation of ADSCs and Retards Intervertebral Disc Degeneration |
| title_short | Genipin Cross-Linked Decellularized Nucleus Pulposus Hydrogel-Like Cell Delivery System Induces Differentiation of ADSCs and Retards Intervertebral Disc Degeneration |
| title_sort | genipin cross linked decellularized nucleus pulposus hydrogel like cell delivery system induces differentiation of adscs and retards intervertebral disc degeneration |
| topic | intervertebral disc degeneration genipin nucleus pulposus ADSC tissue engineering |
| url | https://www.frontiersin.org/articles/10.3389/fbioe.2021.807883/full |
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