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Regulation of extracellular bioactive cations in bone tissue microenvironment induces favorable osteoimmune conditions to accelerate in situ bone regeneration

The design of orthopedic biomaterials has gradually shifted from “immune-friendly” to “immunomodulatory,” in which the biomaterials are able to modulate the inflammatory response via macrophage polarization in a local immune microenvironment that favors osteogenesis and implant-to-bone osseointegrat...

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Autores principales: Lin, Zhengjie, Shen, Danni, Zhou, Weixiao, Zheng, Yufeng, Kong, Tiantian, Liu, Xuanyong, Wu, Shuilin, Chu, Paul K., Zhao, Ying, Wu, Jun, Cheung, Kenneth M.C., Yeung, Kelvin W.K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: KeAi Publishing 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840811/
https://www.ncbi.nlm.nih.gov/pubmed/33553818
http://dx.doi.org/10.1016/j.bioactmat.2021.01.018
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author Lin, Zhengjie
Shen, Danni
Zhou, Weixiao
Zheng, Yufeng
Kong, Tiantian
Liu, Xuanyong
Wu, Shuilin
Chu, Paul K.
Zhao, Ying
Wu, Jun
Cheung, Kenneth M.C.
Yeung, Kelvin W.K.
author_facet Lin, Zhengjie
Shen, Danni
Zhou, Weixiao
Zheng, Yufeng
Kong, Tiantian
Liu, Xuanyong
Wu, Shuilin
Chu, Paul K.
Zhao, Ying
Wu, Jun
Cheung, Kenneth M.C.
Yeung, Kelvin W.K.
author_sort Lin, Zhengjie
collection PubMed
description The design of orthopedic biomaterials has gradually shifted from “immune-friendly” to “immunomodulatory,” in which the biomaterials are able to modulate the inflammatory response via macrophage polarization in a local immune microenvironment that favors osteogenesis and implant-to-bone osseointegration. Despite the well-known effects of bioactive metallic ions on osteogenesis, how extracellular metallic ions manipulate immune cells in bone tissue microenvironments toward osteogenesis and subsequent bone formation has rarely been studied. Herein, we investigate the osteoimmunomodulatory effect of an extracellular bioactive cation (Mg(2+)) in the bone tissue microenvironment using custom-made poly lactic-co-glycolic acid (PLGA)/MgO-alendronate microspheres that endow controllable release of magnesium ions. The results suggest that the Mg(2+)-controlled tissue microenvironment can effectively induce macrophage polarization from the M0 to M2 phenotype via the enhancement of anti-inflammatory (IL-10) and pro-osteogenic (BMP-2 and TGF-β1) cytokines production. It also generates a favorable osteoimmune microenvironment that facilitates the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells. The in vivo results further verify that a large amount of bony tissue, with comparable bone mineral density and mechanical properties, has been generated at an early post-surgical stage in rat intramedullary bone defect models. This study demonstrates that the concept of in situ immunomodulated osteogenesis can be realized in a controlled magnesium tissue microenvironment.
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spelling pubmed-78408112021-02-04 Regulation of extracellular bioactive cations in bone tissue microenvironment induces favorable osteoimmune conditions to accelerate in situ bone regeneration Lin, Zhengjie Shen, Danni Zhou, Weixiao Zheng, Yufeng Kong, Tiantian Liu, Xuanyong Wu, Shuilin Chu, Paul K. Zhao, Ying Wu, Jun Cheung, Kenneth M.C. Yeung, Kelvin W.K. Bioact Mater Article The design of orthopedic biomaterials has gradually shifted from “immune-friendly” to “immunomodulatory,” in which the biomaterials are able to modulate the inflammatory response via macrophage polarization in a local immune microenvironment that favors osteogenesis and implant-to-bone osseointegration. Despite the well-known effects of bioactive metallic ions on osteogenesis, how extracellular metallic ions manipulate immune cells in bone tissue microenvironments toward osteogenesis and subsequent bone formation has rarely been studied. Herein, we investigate the osteoimmunomodulatory effect of an extracellular bioactive cation (Mg(2+)) in the bone tissue microenvironment using custom-made poly lactic-co-glycolic acid (PLGA)/MgO-alendronate microspheres that endow controllable release of magnesium ions. The results suggest that the Mg(2+)-controlled tissue microenvironment can effectively induce macrophage polarization from the M0 to M2 phenotype via the enhancement of anti-inflammatory (IL-10) and pro-osteogenic (BMP-2 and TGF-β1) cytokines production. It also generates a favorable osteoimmune microenvironment that facilitates the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells. The in vivo results further verify that a large amount of bony tissue, with comparable bone mineral density and mechanical properties, has been generated at an early post-surgical stage in rat intramedullary bone defect models. This study demonstrates that the concept of in situ immunomodulated osteogenesis can be realized in a controlled magnesium tissue microenvironment. KeAi Publishing 2021-01-23 /pmc/articles/PMC7840811/ /pubmed/33553818 http://dx.doi.org/10.1016/j.bioactmat.2021.01.018 Text en © 2021 The Authors. Production and hosting by Elsevier B.V. on behalf of KeAi Communications Co., Ltd. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Lin, Zhengjie
Shen, Danni
Zhou, Weixiao
Zheng, Yufeng
Kong, Tiantian
Liu, Xuanyong
Wu, Shuilin
Chu, Paul K.
Zhao, Ying
Wu, Jun
Cheung, Kenneth M.C.
Yeung, Kelvin W.K.
Regulation of extracellular bioactive cations in bone tissue microenvironment induces favorable osteoimmune conditions to accelerate in situ bone regeneration
title Regulation of extracellular bioactive cations in bone tissue microenvironment induces favorable osteoimmune conditions to accelerate in situ bone regeneration
title_full Regulation of extracellular bioactive cations in bone tissue microenvironment induces favorable osteoimmune conditions to accelerate in situ bone regeneration
title_fullStr Regulation of extracellular bioactive cations in bone tissue microenvironment induces favorable osteoimmune conditions to accelerate in situ bone regeneration
title_full_unstemmed Regulation of extracellular bioactive cations in bone tissue microenvironment induces favorable osteoimmune conditions to accelerate in situ bone regeneration
title_short Regulation of extracellular bioactive cations in bone tissue microenvironment induces favorable osteoimmune conditions to accelerate in situ bone regeneration
title_sort regulation of extracellular bioactive cations in bone tissue microenvironment induces favorable osteoimmune conditions to accelerate in situ bone regeneration
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840811/
https://www.ncbi.nlm.nih.gov/pubmed/33553818
http://dx.doi.org/10.1016/j.bioactmat.2021.01.018
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