Title | Regulation of extracellular bioactive cations in bone tissue microenvironment induces favorable osteoimmune conditions to accelerate in situ bone regeneration |
Authors | 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. |
Affiliation | Shenzhen Univ, Coll Chem & Environm Engn, Shenzhen 518060, Peoples R China Univ Hong Kong, Dept Orthopaed & Traumatol, Hong Kong, Peoples R China Peking Univ, Coll Engn, Dept Mat Sci & Engn, Beijing 100871, Peoples R China Univ Hong Kong, Shenzhen Hosp, Shenzhen Key Lab Innovat Technol Orthopaed Trauma, 1 Haiyuan 1st Rd, Shenzhen, Peoples R China Shenzhen Univ, Sch Med, Dept Biomed Engn, Guangdong Key Lab Biomed Measurements & Ultrasoun, Shenzhen 518060, Peoples R China Chinese Acad Sci, Shanghai Inst Ceram, State Key Lab High Performance Ceram & Superfine, Shanghai 200050, Peoples R China Tianjin Univ, Sch Mat Sci & Engn, Key Lab Adv Ceram & Machining Technol, Minist Educ China, Tianjin 300072, Peoples R China City Univ Hong Kong, Dept Phys, Dept Mat Sci & Engn, Tat Chee Ave, Hong Kong, Peoples R China Chinese Acad Sci, Ctr Human Tissues & Organs Degenerat, Shenzhen Inst Adv Technol, Shenzhen 518055, Peoples R China Southeast Univ, Sch Biol Sci & Med Engn, State Key Lab Bioelect, Nanjing 210096, Peoples R China |
Keywords | NF-KAPPA-B CALCIUM-PHOSPHATE CEMENT OSTEOBLAST DIFFERENTIATION INFLAMMATORY RESPONSES TGF-BETA MAGNESIUM OSTEOGENESIS BIOMATERIALS ALENDRONATE SCAFFOLDS |
Issue Date | Aug-2021 |
Publisher | BIOACTIVE MATERIALS |
Abstract | 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-beta 1) 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. |
URI | http://hdl.handle.net/20.500.11897/614002 |
DOI | 10.1016/j.bioactmat.2021.01.018 |
Indexed | SCI(E) |
Appears in Collections: | 工学院 |