3D-printed titanium implant combined with interleukin 4 regulates ordered macrophage polarization to promote bone regeneration and angiogenesis

Aims: The use of 3D-printed titanium implant (DT) can effectively guide bone regeneration. DT triggers a continuous host immune reaction, including macrophage type 1 polarization, that resists osseointegration. Interleukin 4 (IL4) is a specific cytokine modulating osteogenic capability that switches...

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Main Authors: Da-Wang Zhao, Bing Ren, Hong-Wei Wang, Xiao Zhang, Ming-Zhi Yu, Lei Cheng, Yuan-Hua Sang, Shuai-Shuai Cao, Florian M. Thieringer, Dong Zhang, Yi Wan, Chao Liu
Format: Article
Language:English
Published: The British Editorial Society of Bone & Joint Surgery 2021-07-01
Series:Bone & Joint Research
Subjects:
Online Access:https://online.boneandjoint.org.uk/doi/epdf/10.1302/2046-3758.107.BJR-2020-0334.R4
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author Da-Wang Zhao
Bing Ren
Hong-Wei Wang
Xiao Zhang
Ming-Zhi Yu
Lei Cheng
Yuan-Hua Sang
Shuai-Shuai Cao
Florian M. Thieringer
Dong Zhang
Yi Wan
Chao Liu
author_facet Da-Wang Zhao
Bing Ren
Hong-Wei Wang
Xiao Zhang
Ming-Zhi Yu
Lei Cheng
Yuan-Hua Sang
Shuai-Shuai Cao
Florian M. Thieringer
Dong Zhang
Yi Wan
Chao Liu
author_sort Da-Wang Zhao
collection DOAJ
description Aims: The use of 3D-printed titanium implant (DT) can effectively guide bone regeneration. DT triggers a continuous host immune reaction, including macrophage type 1 polarization, that resists osseointegration. Interleukin 4 (IL4) is a specific cytokine modulating osteogenic capability that switches macrophage polarization type 1 to type 2, and this switch favours bone regeneration. Methods: IL4 at concentrations of 0, 30, and 100 ng/ml was used at day 3 to create a biomimetic environment for bone marrow mesenchymal stromal cell (BMMSC) osteogenesis and macrophage polarization on the DT. The osteogenic and immune responses of BMMSCs and macrophages were evaluated respectively. Results: DT plus 30 ng/ml of IL4 (DT + 30 IL4) from day 3 to day 7 significantly (p < 0.01) enhanced macrophage type 2 polarization and BMMSC osteogenesis compared with the other groups. Local injection of IL4 enhanced new bone formation surrounding the DT. Conclusion: DT + 30 IL4 may switch macrophage polarization at the appropriate timepoints to promote bone regeneration.
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spelling doaj.art-4b24b836d9214c8d8a7f10add12181132022-12-21T18:25:33ZengThe British Editorial Society of Bone & Joint SurgeryBone & Joint Research2046-37582021-07-0110741142410.1302/2046-3758.107.BJR-2020-0334.R43D-printed titanium implant combined with interleukin 4 regulates ordered macrophage polarization to promote bone regeneration and angiogenesisDa-Wang Zhao0Bing Ren1Hong-Wei Wang2Xiao Zhang3Ming-Zhi Yu4Lei Cheng5Yuan-Hua Sang6Shuai-Shuai Cao7Florian M. Thieringer8Dong Zhang9Yi Wan10Chao Liu11Department of Orthopedics, Qilu Hospital of Shandong University, Jinan, ChinaKey Laboratory of High Efficiency and Clean Manufacturing, School of Mechanical Engineering, Shandong University, Jinan, ChinaKey Laboratory of High Efficiency and Clean Manufacturing, School of Mechanical Engineering, Shandong University, Jinan, ChinaKey Laboratory of High Efficiency and Clean Manufacturing, School of Mechanical Engineering, Shandong University, Jinan, ChinaKey Laboratory of High Efficiency and Clean Manufacturing, School of Mechanical Engineering, Shandong University, Jinan, ChinaDepartment of Orthopedics, Qilu Hospital of Shandong University, Jinan, ChinaState Key Laboratory of Crystal Materials, Shandong University, Jinan, Shandong, ChinaMedical Additive Manufacturing Research Group, Department of Biomedical Engineering, University of Basel, Basel, SwitzerlandMedical Additive Manufacturing Research Group, Department of Biomedical Engineering, University of Basel, Basel, SwitzerlandInstitute of Stomatology, Shandong University, Jinan, Shandong, ChinaKey Laboratory of High Efficiency and Clean Manufacturing, School of Mechanical Engineering, Shandong University, Jinan, ChinaInstitute of Stomatology, Shandong University, Jinan, Shandong, ChinaAims: The use of 3D-printed titanium implant (DT) can effectively guide bone regeneration. DT triggers a continuous host immune reaction, including macrophage type 1 polarization, that resists osseointegration. Interleukin 4 (IL4) is a specific cytokine modulating osteogenic capability that switches macrophage polarization type 1 to type 2, and this switch favours bone regeneration. Methods: IL4 at concentrations of 0, 30, and 100 ng/ml was used at day 3 to create a biomimetic environment for bone marrow mesenchymal stromal cell (BMMSC) osteogenesis and macrophage polarization on the DT. The osteogenic and immune responses of BMMSCs and macrophages were evaluated respectively. Results: DT plus 30 ng/ml of IL4 (DT + 30 IL4) from day 3 to day 7 significantly (p < 0.01) enhanced macrophage type 2 polarization and BMMSC osteogenesis compared with the other groups. Local injection of IL4 enhanced new bone formation surrounding the DT. Conclusion: DT + 30 IL4 may switch macrophage polarization at the appropriate timepoints to promote bone regeneration.https://online.boneandjoint.org.uk/doi/epdf/10.1302/2046-3758.107.BJR-2020-0334.R4interleukin 43d-printed titanium implantmacrophage polarization
spellingShingle Da-Wang Zhao
Bing Ren
Hong-Wei Wang
Xiao Zhang
Ming-Zhi Yu
Lei Cheng
Yuan-Hua Sang
Shuai-Shuai Cao
Florian M. Thieringer
Dong Zhang
Yi Wan
Chao Liu
3D-printed titanium implant combined with interleukin 4 regulates ordered macrophage polarization to promote bone regeneration and angiogenesis
Bone & Joint Research
interleukin 4
3d-printed titanium implant
macrophage polarization
title 3D-printed titanium implant combined with interleukin 4 regulates ordered macrophage polarization to promote bone regeneration and angiogenesis
title_full 3D-printed titanium implant combined with interleukin 4 regulates ordered macrophage polarization to promote bone regeneration and angiogenesis
title_fullStr 3D-printed titanium implant combined with interleukin 4 regulates ordered macrophage polarization to promote bone regeneration and angiogenesis
title_full_unstemmed 3D-printed titanium implant combined with interleukin 4 regulates ordered macrophage polarization to promote bone regeneration and angiogenesis
title_short 3D-printed titanium implant combined with interleukin 4 regulates ordered macrophage polarization to promote bone regeneration and angiogenesis
title_sort 3d printed titanium implant combined with interleukin 4 regulates ordered macrophage polarization to promote bone regeneration and angiogenesis
topic interleukin 4
3d-printed titanium implant
macrophage polarization
url https://online.boneandjoint.org.uk/doi/epdf/10.1302/2046-3758.107.BJR-2020-0334.R4
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