一种可拯救 ROS 微环境并引导免疫反应修复骨质疏松性骨缺损的多功能复合水凝胶,Advanced Functional Materials

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一种可拯救 ROS 微环境并引导免疫反应修复骨质疏松性骨缺损的多功能复合水凝胶
Advanced Functional Materials ( IF 18.5 ) Pub Date : 2022-03-16 , DOI: 10.1002/adfm.202201067
Qixin Chen ₁ , Jiaying Li ₁ , Feng Han ₁ , Qingchen Meng ₁ , Huan Wang ₁ , Qiang Wei ₁ , Zexi Li ₁ , Feifei Li ₂ , En Xie ₁ , Xiaoyan Qin ₂ , Song Chen ₁ , Weishan Wang ₃ , Chaoyong Liu ₂ , Bin Li _{1,

3} , Fengxuan Han ₁

Affiliation

骨质疏松症患者的骨修复仍然是一个巨大的挑战，因为他们的损伤部位通常伴有异常水平的炎症和活性氧 (ROS)。ROS 之前在骨缺损中被可视化，以过氧化氢 (H ₂ O _{2 ) 为代表。}本研究进一步观察了骨质疏松动物体内的H ₂ O ₂，发现H ₂ O ₂的表达明显高于正常动物。随后，制备了负载有成纤维细胞活化蛋白抑制剂（FAPi）的二氧化锰（MnO _{2 ）包覆的磷酸钙微球复合水凝胶。}其中，MnO ₂旨在充当先进军队消除H ₂ O ₂并产生氧气，并不断释放FAPi用于调节免疫反应和骨骼形成。体外实验表明，水凝胶可有效降低细胞内 ROS，引导巨噬细胞向 M2 极化，并减轻炎症。此外，水凝胶增强骨生成并抑制破骨细胞生成。动物实验表明，水凝胶可以消除活性氧，调节巨噬细胞，促进骨质疏松性骨缺损的修复。总之，这项研究的结果表明，多管齐下的方法通过拯救 ROS 微环境和引导免疫反应来促进骨质疏松性骨缺损的修复具有很大的前景。

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A Multifunctional Composite Hydrogel That Rescues the ROS Microenvironment and Guides the Immune Response for Repair of Osteoporotic Bone Defects

Bone repair in patients with osteoporosis remains a big challenge because their injury sites are often accompanied by an abnormal level of inflammation and reactive oxygen species (ROS). ROS is previously visualized, represented by hydrogen peroxide (H₂O₂), in the bone defects. In this study, the H₂O₂ in osteoporosis animals is further visualized, and it is found that the expression of H₂O₂ is markedly higher than that in normal animals. Subsequently, a composite hydrogel containing manganese dioxide (MnO₂)-coated calcium phosphate microspheres loaded with fibroblast activating protein inhibitor (FAPi) is prepared. Among them, MnO₂ is designed to act as an advanced army to eliminate H₂O₂ and generate oxygen, and constant release of FAPi is used to regulate the immune response and bone formation. In vitro experiments show that the hydrogels effectively reduce intracellular ROS, guide macrophages toward M2 polarization, and alleviate inflammation. Furthermore, the hydrogels enhance the osteogenesis and inhibit osteoclastogenesis. Animal experiments demonstrate that the hydrogels can eliminate ROS, regulate macrophages, and promote repair of osteoporotic bone defects. Together, the findings from this study imply that the multi-pronged approach holds great promise to promote the repair of osteoporotic bone defects by rescuing the ROS microenvironment and guiding the immune response.

更新日期：2022-03-16

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