Multifunctional Scaffold Comprising Metal–Organic Framework, Hydrogel, and Demineralized Bone Matrix for the Treatment of Steroid-Induced Femoral Head Necrosis
Liangjie Bai
Department of Joint Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021 China
Search for more papers by this authorXiaolei Zhang
Department of Joint Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021 China
Search for more papers by this authorWei Shen
Department of Neurology, Linyi People's Hospital, Shandong University, Linyi, Shandong, 276007 China
Search for more papers by this authorPeng Wang
Department of Joint Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021 China
Search for more papers by this authorXin Yin
Department of Joint Surgery, Linyi People's Hospital, Shandong University, Linyi, Shandong, 276007 China
Search for more papers by this authorJianing Liu
Department of Central Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021 China
Search for more papers by this authorHailun Xu
Department of Joint Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021 China
Search for more papers by this authorCorresponding Author
Bing Liu
Department of Oral and Maxillofacial Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021 China
School of Stomatology, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, 250021 China
Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, 250117 China
E-mail: [email protected]; [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Zhentao Man
Department of Joint Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021 China
Endocrine and Metabolic Diseases Hospital of Shandong First Medical University, Jinan, 250021 China
Shandong Institute of Endocrine and Metabolic Diseases, Jinan, Shandong, 250062 China
College of Sports Medicine and Rehabilitation, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, Shandong, 271016 China
E-mail: [email protected]; [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Wei Li
Department of Joint Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021 China
College of Sports Medicine and Rehabilitation, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, Shandong, 271016 China
E-mail: [email protected]; [email protected]; [email protected]
Search for more papers by this authorLiangjie Bai
Department of Joint Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021 China
Search for more papers by this authorXiaolei Zhang
Department of Joint Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021 China
Search for more papers by this authorWei Shen
Department of Neurology, Linyi People's Hospital, Shandong University, Linyi, Shandong, 276007 China
Search for more papers by this authorPeng Wang
Department of Joint Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021 China
Search for more papers by this authorXin Yin
Department of Joint Surgery, Linyi People's Hospital, Shandong University, Linyi, Shandong, 276007 China
Search for more papers by this authorJianing Liu
Department of Central Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021 China
Search for more papers by this authorHailun Xu
Department of Joint Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021 China
Search for more papers by this authorCorresponding Author
Bing Liu
Department of Oral and Maxillofacial Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021 China
School of Stomatology, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, 250021 China
Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, 250117 China
E-mail: [email protected]; [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Zhentao Man
Department of Joint Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021 China
Endocrine and Metabolic Diseases Hospital of Shandong First Medical University, Jinan, 250021 China
Shandong Institute of Endocrine and Metabolic Diseases, Jinan, Shandong, 250062 China
College of Sports Medicine and Rehabilitation, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, Shandong, 271016 China
E-mail: [email protected]; [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Wei Li
Department of Joint Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021 China
College of Sports Medicine and Rehabilitation, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, Shandong, 271016 China
E-mail: [email protected]; [email protected]; [email protected]
Search for more papers by this authorAbstract
Overproduction of reactive oxygen species (ROS) results in oxidative stress, a critical factor in the pathogenesis of steroid-induced osteonecrosis of the femoral head (SONFH). Excess ROS not only hinders the osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) but also impairs mitochondrial structure and function, resulting in irreversible cellular damage. Herein, a biomimetic multifunctional scaffold comprising Zn-modified metal–organic framework 818 (Zn-MOF-818) loaded with deferoxamine (DFO), gelatin methacryloyl (GelMA) hydrogel, and demineralized bone matrix (DBM) is shown to scavenge excess ROS, promote angiogenesis, and regulate immunity. Introduced Zn significantly enhances the superoxide dismutase- and catalase-like activities of MOF-818, which increases ROS-scavenging efficiency. Zn-MOF-818 disrupts the vicious intracellular cycle of mitochondrial dysfunction and ROS accumulation by enhancing mitophagy, stabilizing mitochondrial function, and upregulating antioxidant genes. Additionally, Zn-MOF-818 facilitates the polarization of macrophages toward the M2 phenotype and alleviates inflammation, creating an advantageous immune microenvironment for osteogenic differentiation of BMSCs. The release of DFO, an activator of the HIF-1α pathway, and Zn2+ from Zn-MOF-818, along with the secretion of various cytokines from DBM (such as bone morphogenetic proteins and vascular endothelial growth factors), enhances angiogenesis and osteogenesis. This scaffold targets multiple factors concurrently, offering a promising new approach for treating SONFH.
Conflict of Interest
The authors declare no conflict of interest.
Open Research
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Supporting Information
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| smll202407758-sup-0001-SuppMat.pdf2.5 MB | Supporting Information |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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