骨整合
间充质干细胞
骨免疫学
化学
细胞生物学
骨组织
骨愈合
巨噬细胞极化
免疫系统
生物医学工程
材料科学
生物物理学
巨噬细胞
体外
免疫学
植入
生物化学
解剖
兰克尔
生物
医学
基因
激活剂(遗传学)
外科
作者
Zhiyun Lin,Danni Shen,Wangxiao Zhou,Yufeng Zheng,Tiantian Kong,Xuanyong Liu,Shuilin Wu,Paul K. Chu,Ying Zhao,Jun Wu,Kenneth M.C. Cheung,K.W.K. Yeung
标识
DOI:10.1016/j.bioactmat.2021.01.018
摘要
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 (Mg2+) 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 Mg2+-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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