Hypoxia‐Mimicking Mediated Macrophage‐Elimination of Erythrocytes Promotes Bone Regeneration via Regulating Integrin αvβ3/Fe2+‐Glycolysis‐Inflammation
Abstract Erythrocytes are the dominant component of a blood clot in terms of volume and number. However, longstanding compacted erythrocytes in blood clots form a physical barrier and make fibrin mesh more anti‐fibrinolytic, thus impeding infiltration of mesenchymal stem cells. The necrosis or lysis...
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Wiley
2024-12-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202403921 |
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| author | Yong Ao Yuanlong Guo Yingye Zhang Lv Xie Ruidi Xia Jieyun Xu Mengru Shi Xiaomeng Gao Xiaoran Yu Zetao Chen |
| author_facet | Yong Ao Yuanlong Guo Yingye Zhang Lv Xie Ruidi Xia Jieyun Xu Mengru Shi Xiaomeng Gao Xiaoran Yu Zetao Chen |
| author_sort | Yong Ao |
| collection | DOAJ |
| description | Abstract Erythrocytes are the dominant component of a blood clot in terms of volume and number. However, longstanding compacted erythrocytes in blood clots form a physical barrier and make fibrin mesh more anti‐fibrinolytic, thus impeding infiltration of mesenchymal stem cells. The necrosis or lysis of erythrocytes that are not removed timely can also lead to the release of pro‐inflammatory toxic metabolites, interfering with bone regeneration. Proper bio‐elimination of erythrocytes is essential for an undisturbed bone regeneration process. Here, hypoxia‐mimicking is applied to enhance macrophage‐elimination of erythrocytes. The effect of macrophage‐elimination of erythrocytes on the macrophage intracellular reaction, bone regenerative microenvironment, and bone regeneration outcome is investigated. Results show that the hypoxia‐mimicking agent dimethyloxalylglycine successfully enhances erythrophagocytosis by macrophages in a dose‐dependent manner primarily by up‐regulating the expression of integrin αvβ3. Increased phagocytosed erythrocytes then regulate macrophage intracellular Fe2+‐glycolysis‐inflammation, creating an improved bone regenerative microenvironment characterized by loose fibrin meshes with down‐regulated local inflammatory responses in vivo, thus effectively promoting early osteogenesis and ultimate bone generation. Modulating macrophage‐elimination of erythrocytes can be a promising strategy for eradicating erythrocyte‐caused bone regeneration hindrance and offers a new direction for advanced biomaterial development focusing on the bio‐elimination of erythrocytes. |
| format | Article |
| id | doaj-art-01d8e6367dde4e758fbad5860e10aebb |
| institution | OA Journals |
| issn | 2198-3844 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-01d8e6367dde4e758fbad5860e10aebb2025-08-20T02:19:01ZengWileyAdvanced Science2198-38442024-12-011145n/an/a10.1002/advs.202403921Hypoxia‐Mimicking Mediated Macrophage‐Elimination of Erythrocytes Promotes Bone Regeneration via Regulating Integrin αvβ3/Fe2+‐Glycolysis‐InflammationYong Ao0Yuanlong Guo1Yingye Zhang2Lv Xie3Ruidi Xia4Jieyun Xu5Mengru Shi6Xiaomeng Gao7Xiaoran Yu8Zetao Chen9Hospital of Stomatology Guanghua School of Stomatology Sun Yat‐sen University Guangdong Research Center for Dental and Cranial Rehabilitation and Material Engineering Guangzhou 510055 ChinaHospital of Stomatology Guanghua School of Stomatology Sun Yat‐sen University Guangdong Research Center for Dental and Cranial Rehabilitation and Material Engineering Guangzhou 510055 ChinaHospital of Stomatology Guanghua School of Stomatology Sun Yat‐sen University Guangdong Research Center for Dental and Cranial Rehabilitation and Material Engineering Guangzhou 510055 ChinaHospital of Stomatology Guanghua School of Stomatology Sun Yat‐sen University Guangdong Research Center for Dental and Cranial Rehabilitation and Material Engineering Guangzhou 510055 ChinaHospital of Stomatology Guanghua School of Stomatology Sun Yat‐sen University Guangdong Research Center for Dental and Cranial Rehabilitation and Material Engineering Guangzhou 510055 ChinaHospital of Stomatology Guanghua School of Stomatology Sun Yat‐sen University Guangdong Research Center for Dental and Cranial Rehabilitation and Material Engineering Guangzhou 510055 ChinaHospital of Stomatology Guanghua School of Stomatology Sun Yat‐sen University Guangdong Research Center for Dental and Cranial Rehabilitation and Material Engineering Guangzhou 510055 ChinaHospital of Stomatology Guanghua School of Stomatology Sun Yat‐sen University Guangdong Research Center for Dental and Cranial Rehabilitation and Material Engineering Guangzhou 510055 ChinaHospital of Stomatology Guanghua School of Stomatology Sun Yat‐sen University Guangdong Research Center for Dental and Cranial Rehabilitation and Material Engineering Guangzhou 510055 ChinaHospital of Stomatology Guanghua School of Stomatology Sun Yat‐sen University Guangdong Research Center for Dental and Cranial Rehabilitation and Material Engineering Guangzhou 510055 ChinaAbstract Erythrocytes are the dominant component of a blood clot in terms of volume and number. However, longstanding compacted erythrocytes in blood clots form a physical barrier and make fibrin mesh more anti‐fibrinolytic, thus impeding infiltration of mesenchymal stem cells. The necrosis or lysis of erythrocytes that are not removed timely can also lead to the release of pro‐inflammatory toxic metabolites, interfering with bone regeneration. Proper bio‐elimination of erythrocytes is essential for an undisturbed bone regeneration process. Here, hypoxia‐mimicking is applied to enhance macrophage‐elimination of erythrocytes. The effect of macrophage‐elimination of erythrocytes on the macrophage intracellular reaction, bone regenerative microenvironment, and bone regeneration outcome is investigated. Results show that the hypoxia‐mimicking agent dimethyloxalylglycine successfully enhances erythrophagocytosis by macrophages in a dose‐dependent manner primarily by up‐regulating the expression of integrin αvβ3. Increased phagocytosed erythrocytes then regulate macrophage intracellular Fe2+‐glycolysis‐inflammation, creating an improved bone regenerative microenvironment characterized by loose fibrin meshes with down‐regulated local inflammatory responses in vivo, thus effectively promoting early osteogenesis and ultimate bone generation. Modulating macrophage‐elimination of erythrocytes can be a promising strategy for eradicating erythrocyte‐caused bone regeneration hindrance and offers a new direction for advanced biomaterial development focusing on the bio‐elimination of erythrocytes.https://doi.org/10.1002/advs.202403921bone regenerationerythrocyte clearancehypoxia‐mimickinginflammatory responsesmacrophage phagocytosis |
| spellingShingle | Yong Ao Yuanlong Guo Yingye Zhang Lv Xie Ruidi Xia Jieyun Xu Mengru Shi Xiaomeng Gao Xiaoran Yu Zetao Chen Hypoxia‐Mimicking Mediated Macrophage‐Elimination of Erythrocytes Promotes Bone Regeneration via Regulating Integrin αvβ3/Fe2+‐Glycolysis‐Inflammation Advanced Science bone regeneration erythrocyte clearance hypoxia‐mimicking inflammatory responses macrophage phagocytosis |
| title | Hypoxia‐Mimicking Mediated Macrophage‐Elimination of Erythrocytes Promotes Bone Regeneration via Regulating Integrin αvβ3/Fe2+‐Glycolysis‐Inflammation |
| title_full | Hypoxia‐Mimicking Mediated Macrophage‐Elimination of Erythrocytes Promotes Bone Regeneration via Regulating Integrin αvβ3/Fe2+‐Glycolysis‐Inflammation |
| title_fullStr | Hypoxia‐Mimicking Mediated Macrophage‐Elimination of Erythrocytes Promotes Bone Regeneration via Regulating Integrin αvβ3/Fe2+‐Glycolysis‐Inflammation |
| title_full_unstemmed | Hypoxia‐Mimicking Mediated Macrophage‐Elimination of Erythrocytes Promotes Bone Regeneration via Regulating Integrin αvβ3/Fe2+‐Glycolysis‐Inflammation |
| title_short | Hypoxia‐Mimicking Mediated Macrophage‐Elimination of Erythrocytes Promotes Bone Regeneration via Regulating Integrin αvβ3/Fe2+‐Glycolysis‐Inflammation |
| title_sort | hypoxia mimicking mediated macrophage elimination of erythrocytes promotes bone regeneration via regulating integrin αvβ3 fe2 glycolysis inflammation |
| topic | bone regeneration erythrocyte clearance hypoxia‐mimicking inflammatory responses macrophage phagocytosis |
| url | https://doi.org/10.1002/advs.202403921 |
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