Regulating Macrophage Polarization in High Glucose Microenvironment Using Lithium-Modified Bioglass-Hydrogel for Diabetic Bone Regeneration,Advanced Healthcare Materials

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Regulating Macrophage Polarization in High Glucose Microenvironment Using Lithium-Modified Bioglass-Hydrogel for Diabetic Bone Regeneration
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2022-04-07 , DOI: 10.1002/adhm.202200298
Zerui Wu _{1,

2} , Jiaxiang Bai ₂ , Gaoran Ge ₂ , Tao Wang _{3,

4} , Shuo Feng ₁ , Qiaoqiao Ma ₁ , Xiaolong Liang ₂ , Wenming Li ₂ , Wei Zhang ₂ , Yaozeng Xu ₂ , Kaijin Guo ₁ , Wenguo Cui ₄ , Guochun Zha ₁ , Dechun Geng ₂

Affiliation

Diabetes mellitus is a chronic metabolic disease with a proinflammatory microenvironment, causing poor vascularization and bone regeneration. Due to the lack of effective therapy and one-sided focus on the direct angiogenic properties of biomaterials and osteogenesis stimulation, the treatment of diabetic bone defect remains challenging and complex. In this study, using gelatin methacryloyl (GelMA) as a template, a lithium (Li) -modified bioglass-hydrogel for diabetic bone regeneration is developed. It exhibits a sustained ion release for better bone regeneration under diabetic microenvironment. The hydrogel is shown to be mechanically adaptable to the complex shape of the defect. In vitro, Li-modified bioglass-hydrogel promoted cell proliferation, direct osteogenesis, and regulated macrophages in high glucose (HG) microenvironment, with the secretion of bone morphogenetic protein-2 and vascular endothelial growth factor to stimulate osteogenesis and neovascularization indirectly. In vivo, composite hydrogels containing GelMA and Li-MBG (GM/M-Li) release Li ions to relieve inflammation, providing an anti-inflammatory microenvironment for osteogenesis and angiogenesis. Applying Li-modified bioglass-hydrogel, significantly enhances bone regeneration in a diabetic rat bone defect. Together, both remarkable in vitro and in vivo outcomes in this study present an opportunity for diabetic bone regeneration on the basis of HG microenvironment.

中文翻译：

使用锂改性生物玻璃水凝胶调节高葡萄糖微环境中的巨噬细胞极化用于糖尿病骨再生

糖尿病是一种慢性代谢性疾病，具有促炎微环境，导致血管形成和骨再生不良。由于缺乏有效的治疗方法和片面关注生物材料的直接血管生成特性和成骨刺激，糖尿病骨缺损的治疗仍然具有挑战性和复杂性。在这项研究中，以明胶甲基丙烯酰 (GelMA) 为模板，开发了一种用于糖尿病骨再生的锂 (Li) 改性生物玻璃水凝胶。它表现出持续的离子释放，可在糖尿病微环境下实现更好的骨再生。水凝胶被证明可以机械地适应缺陷的复杂形状。在体外，锂修饰的生物玻璃水凝胶在高葡萄糖（HG）微环境中促进细胞增殖、直接成骨和调节巨噬细胞，通过分泌骨形态发生蛋白-2和血管内皮生长因子间接刺激成骨和新生血管形成。在体内，含有 GelMA 和 Li-MBG (GM/M-Li) 的复合水凝胶释放锂离子以缓解炎症，为成骨和血管生成提供抗炎微环境。应用锂改性生物玻璃水凝胶，显着增强糖尿病大鼠骨缺损的骨再生。总之，本研究中显着的体外和体内结果为基于 HG 微环境的糖尿病骨再生提供了机会。为成骨和血管生成提供抗炎微环境。应用锂改性生物玻璃水凝胶，显着增强糖尿病大鼠骨缺损的骨再生。总之，本研究中显着的体外和体内结果为基于 HG 微环境的糖尿病骨再生提供了机会。为成骨和血管生成提供抗炎微环境。应用锂改性生物玻璃水凝胶，显着增强糖尿病大鼠骨缺损的骨再生。总之，本研究中显着的体外和体内结果为基于 HG 微环境的糖尿病骨再生提供了机会。

更新日期：2022-04-07

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