Immunomodulation with M2 macrophage–derived extracellular vesicles for enhanced titanium implant osseointegration under diabetic conditions

M2 macrophage–derived extracellular vesicles (M2-EVs) demonstrate the capacity to reduce pro-inflammatory M1 macrophage formation, thereby restoring the M1–M2 macrophage balance and promoting immunoregulation. However, the efficacy of M2-EVs in regulating macrophage polarization and subsequently enh...

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Main Authors: Yuzhao Cheng, Xin Dong, Jing Shi, Guangsheng Wu, Pei Tao, Nan Ren, Yimin Zhao, Fenglan Li, Zhongshan Wang
Format: Article
Language:English
Published: Elsevier 2025-02-01
Series:Materials Today Bio
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Online Access:http://www.sciencedirect.com/science/article/pii/S2590006424004460
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author Yuzhao Cheng
Xin Dong
Jing Shi
Guangsheng Wu
Pei Tao
Nan Ren
Yimin Zhao
Fenglan Li
Zhongshan Wang
author_facet Yuzhao Cheng
Xin Dong
Jing Shi
Guangsheng Wu
Pei Tao
Nan Ren
Yimin Zhao
Fenglan Li
Zhongshan Wang
author_sort Yuzhao Cheng
collection DOAJ
description M2 macrophage–derived extracellular vesicles (M2-EVs) demonstrate the capacity to reduce pro-inflammatory M1 macrophage formation, thereby restoring the M1–M2 macrophage balance and promoting immunoregulation. However, the efficacy of M2-EVs in regulating macrophage polarization and subsequently enhancing osseointegration around titanium (Ti) implants in patients with diabetes mellitus (DM) remains to be elucidated. In this study, Ti implants were coated with polydopamine to facilitate M2-EVs adherence. In vitro experiment results demonstrated that M2-EVs could carry miR-23a-3p, inhibiting NOD-like receptor protein3(NLRP3) inflammasome activation in M1 macrophage and reducing the levels of inflammatory cytokines such as IL-1β by targeting NEK7. This improved the M1–M2 macrophage balance and enhanced mineralization on the Ti implant surfaces. The in vivo experiment results demonstrated that in diabetic conditions, the nanocoated M2-EVs significantly promoted high-quality bone deposition around the Ti implants. The current results provide a novel perspective for simple and effective decoration of M2-EVs on Ti implants; clinically, the method may afford osteoimmunomodulatory effects enhancing implant osseointegration in patients with DM.
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spelling doaj-art-92f9a85a6feb41919d68a056c51c2e9e2025-01-17T04:52:03ZengElsevierMaterials Today Bio2590-00642025-02-0130101385Immunomodulation with M2 macrophage–derived extracellular vesicles for enhanced titanium implant osseointegration under diabetic conditionsYuzhao Cheng0Xin Dong1Jing Shi2Guangsheng Wu3Pei Tao4Nan Ren5Yimin Zhao6Fenglan Li7Zhongshan Wang8The Stomatology Department of Shanxi Provincial People Hospital, Shanxi Medical University, Taiyuan, Shanxi, 030001, China; State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Department of Prosthodontics, School of Stomatology, The Fourth Military Medical University, ChinaDepartment of Orthopedic Surgery, Tangdu Hospital, Air Force Military Medical University, Xi'an, Shaanxi Province, ChinaThe Stomatology Department of Shanxi Provincial People Hospital, Shanxi Medical University, Taiyuan, Shanxi, 030001, ChinaState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Department of Prosthodontics, School of Stomatology, The Fourth Military Medical University, China; Department of Stomatology, Qingdao Special Servicemen Recuperation Center of PLA Navy, No.18 Yueyang Road, Qingdao, 266071, ChinaState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Department of Prosthodontics, School of Stomatology, The Fourth Military Medical University, China; College of Chemistry and Bio-engineering, Yichun University, Yichun, Jiangxi, 336000, ChinaState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Department of Prosthodontics, School of Stomatology, The Fourth Military Medical University, ChinaState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Department of Prosthodontics, School of Stomatology, The Fourth Military Medical University, China; Corresponding author. State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Department of Prosthodontics,School of Stomatology, The Fourth Military Medical University, China.The Stomatology Department of Shanxi Provincial People Hospital, Shanxi Medical University, Taiyuan, Shanxi, 030001, China; Corresponding author. The Stomatology Department of Shanxi Provincial People Hospital,Shanxi Medical University, Taiyuan, Shanxi, 030001, China.State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Department of Prosthodontics, School of Stomatology, The Fourth Military Medical University, China; Corresponding author. State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Department of Prosthodontics, School of Stomatology, The Fourth Military Medical University, China.M2 macrophage–derived extracellular vesicles (M2-EVs) demonstrate the capacity to reduce pro-inflammatory M1 macrophage formation, thereby restoring the M1–M2 macrophage balance and promoting immunoregulation. However, the efficacy of M2-EVs in regulating macrophage polarization and subsequently enhancing osseointegration around titanium (Ti) implants in patients with diabetes mellitus (DM) remains to be elucidated. In this study, Ti implants were coated with polydopamine to facilitate M2-EVs adherence. In vitro experiment results demonstrated that M2-EVs could carry miR-23a-3p, inhibiting NOD-like receptor protein3(NLRP3) inflammasome activation in M1 macrophage and reducing the levels of inflammatory cytokines such as IL-1β by targeting NEK7. This improved the M1–M2 macrophage balance and enhanced mineralization on the Ti implant surfaces. The in vivo experiment results demonstrated that in diabetic conditions, the nanocoated M2-EVs significantly promoted high-quality bone deposition around the Ti implants. The current results provide a novel perspective for simple and effective decoration of M2-EVs on Ti implants; clinically, the method may afford osteoimmunomodulatory effects enhancing implant osseointegration in patients with DM.http://www.sciencedirect.com/science/article/pii/S2590006424004460Ti implantsDiabetes mellitusOsseointegrationMacrophageNLRP3 inflammasome
spellingShingle Yuzhao Cheng
Xin Dong
Jing Shi
Guangsheng Wu
Pei Tao
Nan Ren
Yimin Zhao
Fenglan Li
Zhongshan Wang
Immunomodulation with M2 macrophage–derived extracellular vesicles for enhanced titanium implant osseointegration under diabetic conditions
Materials Today Bio
Ti implants
Diabetes mellitus
Osseointegration
Macrophage
NLRP3 inflammasome
title Immunomodulation with M2 macrophage–derived extracellular vesicles for enhanced titanium implant osseointegration under diabetic conditions
title_full Immunomodulation with M2 macrophage–derived extracellular vesicles for enhanced titanium implant osseointegration under diabetic conditions
title_fullStr Immunomodulation with M2 macrophage–derived extracellular vesicles for enhanced titanium implant osseointegration under diabetic conditions
title_full_unstemmed Immunomodulation with M2 macrophage–derived extracellular vesicles for enhanced titanium implant osseointegration under diabetic conditions
title_short Immunomodulation with M2 macrophage–derived extracellular vesicles for enhanced titanium implant osseointegration under diabetic conditions
title_sort immunomodulation with m2 macrophage derived extracellular vesicles for enhanced titanium implant osseointegration under diabetic conditions
topic Ti implants
Diabetes mellitus
Osseointegration
Macrophage
NLRP3 inflammasome
url http://www.sciencedirect.com/science/article/pii/S2590006424004460
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