Implantable Multifunctional Micro‐Oxygen Reservoir System for Promoting Vascular‐Osteogenesis via Remodeling Regenerative Microenvironment
Abstract Hypoxia and reactive oxygen species (ROS) overaccumulation cause persistent oxidative stress and impair intrinsic regenerative potential upon tissue injury. For local tissue injury with hypoxia, such as bone fracture and defects, a localized‐sufficient oxygen supply is highly desirable but...
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2025-01-01
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| Online Access: | https://doi.org/10.1002/advs.202409636 |
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| author | Min Rui Jiannan Mao Hongshuai Wu Yujian Hui Hao Shen Yilin Yang Tao Ma Kewei Ren Juan Wang Wenguo Cui Qin Shi Huilin Yang |
| author_facet | Min Rui Jiannan Mao Hongshuai Wu Yujian Hui Hao Shen Yilin Yang Tao Ma Kewei Ren Juan Wang Wenguo Cui Qin Shi Huilin Yang |
| author_sort | Min Rui |
| collection | DOAJ |
| description | Abstract Hypoxia and reactive oxygen species (ROS) overaccumulation cause persistent oxidative stress and impair intrinsic regenerative potential upon tissue injury. For local tissue injury with hypoxia, such as bone fracture and defects, a localized‐sufficient oxygen supply is highly desirable but remains challenging. Therefore, to explore a strategy and its intrinsic mechanism for supplying oxygen locally and remodeling the regenerative microenvironment, an innovative oxygenating hydrogel microsphere system with sustained oxygenation and antioxidant properties is introduced by loading CaO2@SiO2@PDA (CSP) nanoparticles. Specifically, the CSP nanoparticles exhibited broad‐spectrum free radicals scavenging ability, along with prolonged controlled‐release of oxygen once integrated into the gelatin methacrylate anhydride (GelMA) microspheres (CSP‐GM). The CSP‐GM with extra cellular matrix (ECM)‐mimicking structures reconstructed living niches, promoting the adhesion and proliferation of bone marrow stromal cells (BMSCs). As a multifaceted microenvironment regulator, CSP‐GM remodeled the regenerative microenvironment by synergistically producing oxygen and scavenging ROS, recovering mitochondrial homeostasis and antioxidant defenses of BMSCs, promoting angiogenesis and osteogenesis under hypoxia conditions via precisely modulating the Nrf2/HO‐1 signaling pathway. The multiple pro‐regenerative effects of the implantable functionalized micro‐oxygen reservoir on bone repair are further corroborated by the enhanced vascularized bone formation in rat femoral defects, presenting a comprehensive and promising strategy for tissue repair. |
| format | Article |
| id | doaj-art-07f6ca711342490d8830780d75b7622b |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
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| series | Advanced Science |
| spelling | doaj-art-07f6ca711342490d8830780d75b7622b2025-01-20T13:04:18ZengWileyAdvanced Science2198-38442025-01-01123n/an/a10.1002/advs.202409636Implantable Multifunctional Micro‐Oxygen Reservoir System for Promoting Vascular‐Osteogenesis via Remodeling Regenerative MicroenvironmentMin Rui0Jiannan Mao1Hongshuai Wu2Yujian Hui3Hao Shen4Yilin Yang5Tao Ma6Kewei Ren7Juan Wang8Wenguo Cui9Qin Shi10Huilin Yang11Department of Orthopaedics The First Affiliated Hospital of Soochow University Orthopaedic Institute of Soochow University 899 Pinghai Road Suzhou Jiangsu 215031 P. R. ChinaDepartment of Orthopaedics The First Affiliated Hospital of Soochow University Orthopaedic Institute of Soochow University 899 Pinghai Road Suzhou Jiangsu 215031 P. R. ChinaDepartment of Orthopaedics Wuxi Key Laboratory of Biomaterials for Clinical Application Department of Central Laboratory Jiangyin Clinical College of Xuzhou Medical University No.163 Shoushan Road Jiangyin Jiangsu 214400 P. R. ChinaDepartment of Orthopaedics The First Affiliated Hospital of Soochow University Orthopaedic Institute of Soochow University 899 Pinghai Road Suzhou Jiangsu 215031 P. R. ChinaDepartment of Orthopaedics The First Affiliated Hospital of Soochow University Orthopaedic Institute of Soochow University 899 Pinghai Road Suzhou Jiangsu 215031 P. R. ChinaDepartment of Orthopaedics The First Affiliated Hospital of Soochow University Orthopaedic Institute of Soochow University 899 Pinghai Road Suzhou Jiangsu 215031 P. R. ChinaDepartment of Orthopedics The First Affiliated Hospital of Wannan Medical College Yijishan Hospital, No. 2, Zhe Shan Xi Road Wuhu Anhui 241001 P. R. ChinaDepartment of Orthopaedics Wuxi Key Laboratory of Biomaterials for Clinical Application Department of Central Laboratory Jiangyin Clinical College of Xuzhou Medical University No.163 Shoushan Road Jiangyin Jiangsu 214400 P. R. ChinaDepartment of Orthopaedics Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases Shanghai Institute of Traumatology and Orthopaedics Ruijin Hospital Shanghai Jiao Tong University School of Medicine 197 Ruijin 2nd Road Shanghai 200025 P. R. ChinaDepartment of Orthopaedics Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases Shanghai Institute of Traumatology and Orthopaedics Ruijin Hospital Shanghai Jiao Tong University School of Medicine 197 Ruijin 2nd Road Shanghai 200025 P. R. ChinaDepartment of Orthopaedics The First Affiliated Hospital of Soochow University Orthopaedic Institute of Soochow University 899 Pinghai Road Suzhou Jiangsu 215031 P. R. ChinaDepartment of Orthopaedics The First Affiliated Hospital of Soochow University Orthopaedic Institute of Soochow University 899 Pinghai Road Suzhou Jiangsu 215031 P. R. ChinaAbstract Hypoxia and reactive oxygen species (ROS) overaccumulation cause persistent oxidative stress and impair intrinsic regenerative potential upon tissue injury. For local tissue injury with hypoxia, such as bone fracture and defects, a localized‐sufficient oxygen supply is highly desirable but remains challenging. Therefore, to explore a strategy and its intrinsic mechanism for supplying oxygen locally and remodeling the regenerative microenvironment, an innovative oxygenating hydrogel microsphere system with sustained oxygenation and antioxidant properties is introduced by loading CaO2@SiO2@PDA (CSP) nanoparticles. Specifically, the CSP nanoparticles exhibited broad‐spectrum free radicals scavenging ability, along with prolonged controlled‐release of oxygen once integrated into the gelatin methacrylate anhydride (GelMA) microspheres (CSP‐GM). The CSP‐GM with extra cellular matrix (ECM)‐mimicking structures reconstructed living niches, promoting the adhesion and proliferation of bone marrow stromal cells (BMSCs). As a multifaceted microenvironment regulator, CSP‐GM remodeled the regenerative microenvironment by synergistically producing oxygen and scavenging ROS, recovering mitochondrial homeostasis and antioxidant defenses of BMSCs, promoting angiogenesis and osteogenesis under hypoxia conditions via precisely modulating the Nrf2/HO‐1 signaling pathway. The multiple pro‐regenerative effects of the implantable functionalized micro‐oxygen reservoir on bone repair are further corroborated by the enhanced vascularized bone formation in rat femoral defects, presenting a comprehensive and promising strategy for tissue repair.https://doi.org/10.1002/advs.202409636bone regenerationhydrogel microspherehypoxiamicroenvironment regulationoxygen generationreactive oxygen species |
| spellingShingle | Min Rui Jiannan Mao Hongshuai Wu Yujian Hui Hao Shen Yilin Yang Tao Ma Kewei Ren Juan Wang Wenguo Cui Qin Shi Huilin Yang Implantable Multifunctional Micro‐Oxygen Reservoir System for Promoting Vascular‐Osteogenesis via Remodeling Regenerative Microenvironment Advanced Science bone regeneration hydrogel microsphere hypoxia microenvironment regulation oxygen generation reactive oxygen species |
| title | Implantable Multifunctional Micro‐Oxygen Reservoir System for Promoting Vascular‐Osteogenesis via Remodeling Regenerative Microenvironment |
| title_full | Implantable Multifunctional Micro‐Oxygen Reservoir System for Promoting Vascular‐Osteogenesis via Remodeling Regenerative Microenvironment |
| title_fullStr | Implantable Multifunctional Micro‐Oxygen Reservoir System for Promoting Vascular‐Osteogenesis via Remodeling Regenerative Microenvironment |
| title_full_unstemmed | Implantable Multifunctional Micro‐Oxygen Reservoir System for Promoting Vascular‐Osteogenesis via Remodeling Regenerative Microenvironment |
| title_short | Implantable Multifunctional Micro‐Oxygen Reservoir System for Promoting Vascular‐Osteogenesis via Remodeling Regenerative Microenvironment |
| title_sort | implantable multifunctional micro oxygen reservoir system for promoting vascular osteogenesis via remodeling regenerative microenvironment |
| topic | bone regeneration hydrogel microsphere hypoxia microenvironment regulation oxygen generation reactive oxygen species |
| url | https://doi.org/10.1002/advs.202409636 |
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