Osteoimmunomodulatory injectable Lithium-Heparin hydrogel with Microspheres/TGF-β1 delivery promotes M2 macrophage polarization and osteogenesis for guided bone regeneration
Osteoimmunomodulatory injectable Lithium-Heparin hydrogel with Microspheres/TGF-β1 delivery promotes M2 macrophage polarization and osteogenesis for guided bone regeneration
复制标题
载有微球/转化生长因子-β1（TGF-β1）的具有骨免疫调节作用的可注射锂-肝素水凝胶可促进M2型巨噬细胞极化和成骨，用于引导骨再生
DOI：
10.1016/j.cej.2022.134991
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发表时间：
2022-02-04
影响因子：
15.1
通讯作者：
Tian, Meng
中科院分区：
文献类型：
--
作者：
Li, Donghai;Yang, Zhouyuan;Tian, Meng
骨损伤发生时，巨噬细胞、中性粒细胞、T淋巴细胞等免疫细胞参与损伤部位的免疫调节和骨动力学调节，操纵免疫细胞产生良好的骨免疫环境是骨修复的一种很有前景的途径。本文报道了一种采用先进的骨免疫调节生物材料平台的骨再生策略，该平台将含有tgf - β 1的明胶-肝素微球（MS/ tgf - β 1）装载到可注射的锂-肝素水凝胶（Li-gel）中，其中Li-凝胶不仅作为MS/ tgf - β 1的递送载体，而且作为促进成骨的Li离子释放基质，而tgf - β 1的释放则引导巨噬细胞M2极化。此外，体外和体内研究均表明Li-gel@MS/ tgf - β 1通过tgf - β /Snail通路促进成骨和血管生成，促进新骨形成。综上所述，这种通过促进M2巨噬细胞极化和成骨引导骨再生的骨免疫调节生物材料平台可能是一种很有前途的骨修复和再生方法。
When bone injury occurs, immune cells including macrophages, neutrophils, and T lymphocytes are recruited and participate in immunomodulatory and bone dynamics regulation in injury sites, and thus manipulate the immune cells to generate a favorable osteo-immune environment is a promising approach for bone repair. Here we report a bone regeneration strategy using an advanced osteoimmunomodulatory biomaterial platform that loads TGF-beta 1-containing gelatin-heparin microspheres (MS/TGF-beta 1) into an injectable lithium-heparin hydrogel (Li-gel), wherein Li-gel acts not only as delivery carrier for MS/TGF-beta 1, but also as Li ions release matrix promoting osteogenesis, while the TGF-beta 1 release is to guide macrophage for M2 polarization. Moreover, both in vitro and in vivo studies show that Li-gel@MS/TGF-beta 1 enhances osteogenesis and angiogenesis via TGF-beta/Snail pathway, and improves the new bone formation. Taken together, this newly developed osteoimmunomodulatory biomaterial platform with guided bone regeneration via promoting M2 macrophage polarization and osteogenesis can be a promising approach for bone repair and regeneration.