Kartogenin‐Loaded Aminated Hollow Mesoporous Prussian Blue Nanozyme‐Reinforced Hydrogel Remodels the Senescent Microenvironment via Reactive Oxygen Species Scavenging and Stimulator of Interferon Genes Inhibition to Promote Cartilage Regeneration
Articular cartilage defects remain an intractable clinical challenge due to the limited capacity of cartilage for self‐renewal and repair. Excessive accumulation of reactive oxygen species (ROS) leads to mitochondrial dysfunction, inflammation, and chondrocyte senescence, impeding cartilage regenera...
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| Format: | Article |
| Language: | English |
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Wiley-VCH
2025-07-01
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| Series: | Small Structures |
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| Online Access: | https://doi.org/10.1002/sstr.202400592 |
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| author | Shu‐Hang He Zhi‐Han Shen Ren Zhang Po‐Lin Liu Xu‐Ran Li Qing‐Song Deng Yu‐Chen Zhang Ang Wang Xiao‐Qiu Dou Shang‐Chun Guo Shi‐Cong Tao |
| author_facet | Shu‐Hang He Zhi‐Han Shen Ren Zhang Po‐Lin Liu Xu‐Ran Li Qing‐Song Deng Yu‐Chen Zhang Ang Wang Xiao‐Qiu Dou Shang‐Chun Guo Shi‐Cong Tao |
| author_sort | Shu‐Hang He |
| collection | DOAJ |
| description | Articular cartilage defects remain an intractable clinical challenge due to the limited capacity of cartilage for self‐renewal and repair. Excessive accumulation of reactive oxygen species (ROS) leads to mitochondrial dysfunction, inflammation, and chondrocyte senescence, impeding cartilage regeneration. In this study, we developed an injectable, dual‐function hydrogel system comprising kartogenin (KGN)‐loaded aminated hollow mesoporous Prussian blue (NH2‐HMPB) nanozyme (termed NH@K nanozyme) and hyaluronic acid methacrylate (HAMA). This “double sustained‐release” system prolongs the therapeutic duration of KGN while seamlessly filling irregular cartilage defects. As NH@K nanozyme is released, it scavenges ROS, reduces oxidative stress, protects mitochondrial function, inhibits cyclic GMP‐AMP synthase–stimulator of interferon genes (STING) pathway activation, and modulates inflammation and macrophage polarization, rejuvenating the senescent microenvironment. RNA sequencing analysis and in vitro experiments revealed that NH@K nanozyme modulates signaling pathways associated with chondrogenesis and inflammation, promoting cartilage repair. In a rat model, HAMA‐NH@K hydrogel significantly enhances extracellular matrix deposition and cartilage regeneration. The synergistic combination of nanozyme and hydrogel in our system enables the reshaping of the senescent microenvironment, providing a promising strategy for advanced cartilage regeneration. |
| format | Article |
| id | doaj-art-baa723ebcc244595a5ebca4fbbfdcc93 |
| institution | Kabale University |
| issn | 2688-4062 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Wiley-VCH |
| record_format | Article |
| series | Small Structures |
| spelling | doaj-art-baa723ebcc244595a5ebca4fbbfdcc932025-08-20T03:33:07ZengWiley-VCHSmall Structures2688-40622025-07-0167n/an/a10.1002/sstr.202400592Kartogenin‐Loaded Aminated Hollow Mesoporous Prussian Blue Nanozyme‐Reinforced Hydrogel Remodels the Senescent Microenvironment via Reactive Oxygen Species Scavenging and Stimulator of Interferon Genes Inhibition to Promote Cartilage RegenerationShu‐Hang He0Zhi‐Han Shen1Ren Zhang2Po‐Lin Liu3Xu‐Ran Li4Qing‐Song Deng5Yu‐Chen Zhang6Ang Wang7Xiao‐Qiu Dou8Shang‐Chun Guo9Shi‐Cong Tao10Department of Orthopedic Surgery Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine 600 Yishan Road Shanghai 200233 ChinaDepartment of Orthopedic Surgery Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine 600 Yishan Road Shanghai 200233 ChinaDepartment of Postgraduate Jiangxi University of Chinese Medicine 1688 Meiling Avenue Jiangxi Nanchang 330004 ChinaDepartment of Orthopedic Surgery Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine 600 Yishan Road Shanghai 200233 ChinaShanghai Key Laboratory of Orthopedic Implants Department of Orthopedic Surgery Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine 639 Zhizaoju Road Shanghai 200001 ChinaDepartment of Orthopedic Surgery Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine 600 Yishan Road Shanghai 200233 ChinaGeneral Practice Training Base The First Affiliated Hospital of Naval Medical University (Second Military Medical University) 168 Changhai Road Shanghai 200433 ChinaSchool of Medicine Shanghai Jiao Tong University 227 South Chongqing Road Shanghai 200240 ChinaState Key Lab of Metal Matrix Composites School of Materials Science and Engineering Shanghai Jiao Tong University Shanghai 200240 ChinaDepartment of Orthopedic Surgery Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine 600 Yishan Road Shanghai 200233 ChinaDepartment of Orthopedic Surgery Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine 600 Yishan Road Shanghai 200233 ChinaArticular cartilage defects remain an intractable clinical challenge due to the limited capacity of cartilage for self‐renewal and repair. Excessive accumulation of reactive oxygen species (ROS) leads to mitochondrial dysfunction, inflammation, and chondrocyte senescence, impeding cartilage regeneration. In this study, we developed an injectable, dual‐function hydrogel system comprising kartogenin (KGN)‐loaded aminated hollow mesoporous Prussian blue (NH2‐HMPB) nanozyme (termed NH@K nanozyme) and hyaluronic acid methacrylate (HAMA). This “double sustained‐release” system prolongs the therapeutic duration of KGN while seamlessly filling irregular cartilage defects. As NH@K nanozyme is released, it scavenges ROS, reduces oxidative stress, protects mitochondrial function, inhibits cyclic GMP‐AMP synthase–stimulator of interferon genes (STING) pathway activation, and modulates inflammation and macrophage polarization, rejuvenating the senescent microenvironment. RNA sequencing analysis and in vitro experiments revealed that NH@K nanozyme modulates signaling pathways associated with chondrogenesis and inflammation, promoting cartilage repair. In a rat model, HAMA‐NH@K hydrogel significantly enhances extracellular matrix deposition and cartilage regeneration. The synergistic combination of nanozyme and hydrogel in our system enables the reshaping of the senescent microenvironment, providing a promising strategy for advanced cartilage regeneration.https://doi.org/10.1002/sstr.202400592cartilage regenerationnanozyme‐reinforced hydrogelreactive oxygen species scavengingsenescent microenvironmentstimulator of interferon genes inhibition |
| spellingShingle | Shu‐Hang He Zhi‐Han Shen Ren Zhang Po‐Lin Liu Xu‐Ran Li Qing‐Song Deng Yu‐Chen Zhang Ang Wang Xiao‐Qiu Dou Shang‐Chun Guo Shi‐Cong Tao Kartogenin‐Loaded Aminated Hollow Mesoporous Prussian Blue Nanozyme‐Reinforced Hydrogel Remodels the Senescent Microenvironment via Reactive Oxygen Species Scavenging and Stimulator of Interferon Genes Inhibition to Promote Cartilage Regeneration Small Structures cartilage regeneration nanozyme‐reinforced hydrogel reactive oxygen species scavenging senescent microenvironment stimulator of interferon genes inhibition |
| title | Kartogenin‐Loaded Aminated Hollow Mesoporous Prussian Blue Nanozyme‐Reinforced Hydrogel Remodels the Senescent Microenvironment via Reactive Oxygen Species Scavenging and Stimulator of Interferon Genes Inhibition to Promote Cartilage Regeneration |
| title_full | Kartogenin‐Loaded Aminated Hollow Mesoporous Prussian Blue Nanozyme‐Reinforced Hydrogel Remodels the Senescent Microenvironment via Reactive Oxygen Species Scavenging and Stimulator of Interferon Genes Inhibition to Promote Cartilage Regeneration |
| title_fullStr | Kartogenin‐Loaded Aminated Hollow Mesoporous Prussian Blue Nanozyme‐Reinforced Hydrogel Remodels the Senescent Microenvironment via Reactive Oxygen Species Scavenging and Stimulator of Interferon Genes Inhibition to Promote Cartilage Regeneration |
| title_full_unstemmed | Kartogenin‐Loaded Aminated Hollow Mesoporous Prussian Blue Nanozyme‐Reinforced Hydrogel Remodels the Senescent Microenvironment via Reactive Oxygen Species Scavenging and Stimulator of Interferon Genes Inhibition to Promote Cartilage Regeneration |
| title_short | Kartogenin‐Loaded Aminated Hollow Mesoporous Prussian Blue Nanozyme‐Reinforced Hydrogel Remodels the Senescent Microenvironment via Reactive Oxygen Species Scavenging and Stimulator of Interferon Genes Inhibition to Promote Cartilage Regeneration |
| title_sort | kartogenin loaded aminated hollow mesoporous prussian blue nanozyme reinforced hydrogel remodels the senescent microenvironment via reactive oxygen species scavenging and stimulator of interferon genes inhibition to promote cartilage regeneration |
| topic | cartilage regeneration nanozyme‐reinforced hydrogel reactive oxygen species scavenging senescent microenvironment stimulator of interferon genes inhibition |
| url | https://doi.org/10.1002/sstr.202400592 |
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