Periosteal matrix-derived hydrogel promotes bone repair through an early immune regulation coupled with enhanced angio- and osteogenesis
Periosteal matrix-derived hydrogel promotes bone repair through an early immune regulation coupled with enhanced angio- and osteogenesis
复制标题
骨膜基质衍生的水凝胶通过早期免疫调节以及增强的血管生成和成骨作用来促进骨修复。
DOI：
10.1016/j.biomaterials.2019.119552
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发表时间：
2020-01-01
期刊：
影响因子：
14
通讯作者：
Fan, Shunwu
中科院分区：
文献类型：
--
作者：
Qiu, Pengcheng;Li, Mobai;Fan, Shunwu
骨愈合是一个复杂的生理过程，由炎症免疫的早期调节启动，涉及血管生成、成骨分化和生物矿化等多个过程。在这里，我们制造了一种可注射的骨膜细胞外基质(PEM)水凝胶，它动态地整合了多种生物功能，因此在骨折愈合过程的不同阶段发挥作用。与I型胶原水凝胶相比，PEM水凝胶得到了充分的表征。在体外实验中评估了PEM水凝胶对愈合过程不同阶段的影响。PEM水凝胶诱导巨噬细胞募集和M2极化，促进MSCs向内皮样细胞分化，HUVEC管的形成，原代成骨细胞和MSCs的成骨分化，以及模拟体液浸泡后的矿化。利用大鼠临界大小的颅骨缺损模型，评估了水凝胶的动态和多相效应。在修复的早期阶段，PEM水凝胶促进了巨噬细胞从M1到M2的转变。随着骨修复的进行，PEM水凝胶促进了血管的迁移、相对较大血管的发展和功能性血管的形成。这些效应也在皮下植入模型中得到了验证。最终，PEM水凝胶比I型胶原水凝胶更能促进大骨缺损处的成熟骨形成。这些生物效应与骨骼再生的自然过程很好地协调。因此，PEM水凝胶有望成为骨组织工程的生物材料。
Bone healing is a complex physiological process initiated by early regulation of the inflammatory immunity and entails multiple events including angiogenesis, osteogenic differentiation, and biomineralization. Here, we fabricated an injectable periosteal extracellular matrix (PEM) hydrogel that dynamically integrates multiple biological functions and, therefore, acts at different stages of the fracture healing process. PEM hydrogels were fully characterized compared with a collagen I hydrogel. The effects of PEM hydrogels on the different phases of the healing process were assessed in vitro. PEM hydrogels induced the recruitment and M2-polarization of macrophages, promoted the differentiation of MSCs into endothelial-like cells, HUVEC tube formation, osteogenic differentiation of primary calvarial osteoblasts and MSCs, and mineralization after being immersed in simulated body fluid. The dynamic and multiphase effects of the hydrogels were evaluated using a rat critical-sized calvarial defect model in vivo. During the early phase of repair, PEM hydrogels facilitated the M1-to-M2 transition of macrophages. As bone repair progressed, PEM hydrogels promoted blood vessel migration, the development of relative larger blood vessels, and functional vascularization. These effects were also verified in a subcutaneous embedding model. Eventually, PEM hydrogels promoted mature bone formation in large bone defects to a greater extent than collagen I hydrogels. These biological effects coordinated well with the natural process of bone regeneration. Thus, PEM hydrogels may serve as promising biomaterials in bone tissue engineering.