A miR-activated hydrogel for the delivery of a pro-chondrogenic microRNA-221 inhibitor as a minimally invasive therapeutic approach for articular cartilage repair
Articular cartilage has limited capacity for repair (or for regeneration) under pathological conditions, given its non-vascularized connective tissue structure and low cellular density. Our group has successfully developed an injectable hydrogel for cartilage repair, composed of collagen type I (Col...
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Elsevier
2025-02-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590006424004435 |
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| author | Shan An Claudio Intini Donagh O'Shea James E. Dixon Yiran Zheng Fergal J. O'Brien |
| author_facet | Shan An Claudio Intini Donagh O'Shea James E. Dixon Yiran Zheng Fergal J. O'Brien |
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| description | Articular cartilage has limited capacity for repair (or for regeneration) under pathological conditions, given its non-vascularized connective tissue structure and low cellular density. Our group has successfully developed an injectable hydrogel for cartilage repair, composed of collagen type I (Col I), collagen type II (Col II), and methacrylated-hyaluronic acid (MeHA), capable of supporting chondrogenic differentiation of mesenchymal stem cells (MSCs) towards articular cartilage-like phenotypes. Recent studies have demonstrated that silencing miR-221 may be an effective approach in promoting improved MSC chondrogenesis. Thus, this study aimed to develop a miR-activated hydrogel capable of offering a more effective and less invasive therapeutic approach to articular cartilage repair by delivering a pro-chondrogenic miR-221 inhibitor to MSCs using our MeHA-Col I/Col II hydrogel. The MeHA-Col I/Col II hydrogel was cast as previously shown and incorporated with cells transfected with miR-221 inhibitor (using a non-viral peptide delivery vector) to produce the miR-activated hydrogel. Down-regulation of miR-221 did not affect cell viability and enhanced MSCs-mediated chondrogenesis, as evidenced by significantly upregulated expression of key pro-chondrogenic articular cartilage genes (COL2A1 and ACAN) without promoting hypertrophic events (RUNX2 and COL10A1). Furthermore, miR-221 down-regulation improved cartilage-like matrix formation in the MeHA-Col I/Col II hydrogel, with significantly higher levels of sulfated glycosaminoglycans (sGAG) and Col II produced by MSCs in the hydrogel. These results provide evidence of the potential of the miR-activated hydrogel as a minimally invasive therapeutic strategy for articular cartilage repair. |
| format | Article |
| id | doaj-art-278ad7e6cfe94660ab328fec28170afe |
| institution | Kabale University |
| issn | 2590-0064 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials Today Bio |
| spelling | doaj-art-278ad7e6cfe94660ab328fec28170afe2025-01-17T04:52:02ZengElsevierMaterials Today Bio2590-00642025-02-0130101382A miR-activated hydrogel for the delivery of a pro-chondrogenic microRNA-221 inhibitor as a minimally invasive therapeutic approach for articular cartilage repairShan An0Claudio Intini1Donagh O'Shea2James E. Dixon3Yiran Zheng4Fergal J. O'Brien5Tissue Engineering Research Group (TERG), Department of Anatomy and Regenerative Medicine, RCSI, Dublin, Ireland; College of Pharmaceutical Sciences, Soochow University, ChinaTissue Engineering Research Group (TERG), Department of Anatomy and Regenerative Medicine, RCSI, Dublin, Ireland; Advanced Materials and Bioengineering Research Centre (AMBER), RCSI and TCD, Dublin, IrelandTissue Engineering Research Group (TERG), Department of Anatomy and Regenerative Medicine, RCSI, Dublin, Ireland; Advanced Materials and Bioengineering Research Centre (AMBER), RCSI and TCD, Dublin, IrelandRegenerative Medicine & Cellular Therapies (RMCT), Biodiscovery Institute (BDI), School of Pharmacy, University of Nottingham, Nottingham, NG7 2RD, UK; NIHR Nottingham Biomedical Research Centre, University of Nottingham, Nottingham, UKCollege of Pharmaceutical Sciences, Soochow University, ChinaTissue Engineering Research Group (TERG), Department of Anatomy and Regenerative Medicine, RCSI, Dublin, Ireland; Advanced Materials and Bioengineering Research Centre (AMBER), RCSI and TCD, Dublin, Ireland; Trinity Centre for Biomedical Engineering, TCD, Ireland; Corresponding author. Tissue Engineering Research Group (TERG), Department of Anatomy and Regenerative Medicine, RCSI, Dublin, Ireland.Articular cartilage has limited capacity for repair (or for regeneration) under pathological conditions, given its non-vascularized connective tissue structure and low cellular density. Our group has successfully developed an injectable hydrogel for cartilage repair, composed of collagen type I (Col I), collagen type II (Col II), and methacrylated-hyaluronic acid (MeHA), capable of supporting chondrogenic differentiation of mesenchymal stem cells (MSCs) towards articular cartilage-like phenotypes. Recent studies have demonstrated that silencing miR-221 may be an effective approach in promoting improved MSC chondrogenesis. Thus, this study aimed to develop a miR-activated hydrogel capable of offering a more effective and less invasive therapeutic approach to articular cartilage repair by delivering a pro-chondrogenic miR-221 inhibitor to MSCs using our MeHA-Col I/Col II hydrogel. The MeHA-Col I/Col II hydrogel was cast as previously shown and incorporated with cells transfected with miR-221 inhibitor (using a non-viral peptide delivery vector) to produce the miR-activated hydrogel. Down-regulation of miR-221 did not affect cell viability and enhanced MSCs-mediated chondrogenesis, as evidenced by significantly upregulated expression of key pro-chondrogenic articular cartilage genes (COL2A1 and ACAN) without promoting hypertrophic events (RUNX2 and COL10A1). Furthermore, miR-221 down-regulation improved cartilage-like matrix formation in the MeHA-Col I/Col II hydrogel, with significantly higher levels of sulfated glycosaminoglycans (sGAG) and Col II produced by MSCs in the hydrogel. These results provide evidence of the potential of the miR-activated hydrogel as a minimally invasive therapeutic strategy for articular cartilage repair.http://www.sciencedirect.com/science/article/pii/S2590006424004435Cartilage repairmiR-221 inhibitorMeHA-Col I/Col II hydrogelGene therapyChondrogenesis |
| spellingShingle | Shan An Claudio Intini Donagh O'Shea James E. Dixon Yiran Zheng Fergal J. O'Brien A miR-activated hydrogel for the delivery of a pro-chondrogenic microRNA-221 inhibitor as a minimally invasive therapeutic approach for articular cartilage repair Materials Today Bio Cartilage repair miR-221 inhibitor MeHA-Col I/Col II hydrogel Gene therapy Chondrogenesis |
| title | A miR-activated hydrogel for the delivery of a pro-chondrogenic microRNA-221 inhibitor as a minimally invasive therapeutic approach for articular cartilage repair |
| title_full | A miR-activated hydrogel for the delivery of a pro-chondrogenic microRNA-221 inhibitor as a minimally invasive therapeutic approach for articular cartilage repair |
| title_fullStr | A miR-activated hydrogel for the delivery of a pro-chondrogenic microRNA-221 inhibitor as a minimally invasive therapeutic approach for articular cartilage repair |
| title_full_unstemmed | A miR-activated hydrogel for the delivery of a pro-chondrogenic microRNA-221 inhibitor as a minimally invasive therapeutic approach for articular cartilage repair |
| title_short | A miR-activated hydrogel for the delivery of a pro-chondrogenic microRNA-221 inhibitor as a minimally invasive therapeutic approach for articular cartilage repair |
| title_sort | mir activated hydrogel for the delivery of a pro chondrogenic microrna 221 inhibitor as a minimally invasive therapeutic approach for articular cartilage repair |
| topic | Cartilage repair miR-221 inhibitor MeHA-Col I/Col II hydrogel Gene therapy Chondrogenesis |
| url | http://www.sciencedirect.com/science/article/pii/S2590006424004435 |
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