Laminin alpha 4 promotes bone regeneration by facilitating cell adhesion and vascularization
Laminin alpha 4 promotes bone regeneration by facilitating cell adhesion and vascularization
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DOI：
10.1016/j.actbio.2021.03.011
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发表时间：
2021-04-29
影响因子：
9.7
通讯作者：
Luo，Fei
中科院分区：
文献类型：
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作者：
Tang，Yong;Luo，Keyu;Luo，Fei
选择性细胞保留技术(SCR)作为一种骨组织工程技术已被广泛应用于骨移植的实时构建。支架中保留的间充质干细胞(MSCs)和内皮祖细胞(EPC)数量越多，支架微环境的成骨和血管生成特性越好。生物支架性能的改善反过来又导致骨移植存活、骨再生和血管生成的改善。层粘连蛋白在细胞-基质黏附、细胞增殖和分化中起关键作用。我们设计了一个含层粘连蛋白α4核心功能氨基酸序列的胶原结合结构域(CBD-LN肽)来补充胶原基脱钙骨基质支架的功能表面。该支架通过上调整合素α5β1和整合素αvβ3的表达，促进骨髓间充质干细胞和内皮祖细胞的早期黏附，从而加速后续细胞的扩散、增殖和分化。有趣的是，随着临床SCR技术的使用，它促进了MSCs(CD90+/CD105+细胞)和EPC(CD31+细胞)在支架中的保留。此外，DBM/CBD-LN支架通过激活HIF-1α信号通路诱导H型血管的形成。DBM/CBD-LN支架在体内表现出快速的骨形成和血管生成，提示它可能作为一种新的生物材料应用于骨组织工程。其中，脱钙骨基质(DBM)是一种应用广泛的SCR临床生物材料，但其黏附性能和血管生成活性较差。在这项工作中，我们设计了一个包含层粘连蛋白α4核心功能氨基酸序列的胶原结合结构域，以补充胶原基支架的功能表面。这种生物支架促进了SCR介导的MSCs和EPC的早期细胞黏附，从而加速了后续细胞的扩散、增殖和分化。我们的结果表明，这种生物支架在体内可以很好地诱导成骨和血管生成。综上所述，该生物支架在SCR中具有良好的应用前景，有望为临床提供高生物活性的植骨材料。
Selective cell retention (SCR) has been widely used as a bone tissue engineering technique for the real-time fabrication of bone grafts. The greater the number of mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) retained in the scaffold, the better the osteoinductive and angiogenic properties of the scaffold's microenvironment. Improved bioscaffold properties in turn lead to improved bone graft survival, bone regeneration, and angiogenesis. Laminin plays a key role in cell-matrix adhesion, cell proliferation, and differentiation. We designed a collagen-binding domain (CBD) containing the core functional amino acid sequences of laminin α4 (CBD-LN peptide) to supplement the functional surface of a collagen-based decalcified bone matrix (DBM) scaffold. This scaffold promoted MSCs and EPCs early cell adhesion through up-regulating the expression of integrin α5β1 and integrin αvβ3 respectively, thus accelerated the following cell spreading, proliferation, and differentiation. Interestingly, it promoted the retention of MSCs (CD90+/CD105+cells) and EPCs (CD31+cells) in the scaffold following the use of clinical SCR technology. Furthermore, the DBM/CBD-LN scaffold induced the formation of type H vessels through the activation of the HIF-1α signaling pathway. The DBM/CBD-LN scaffold displayed rapid bone formation and angiogenesisin vivo, suggesting that it might be used as a new biomaterial in bone tissue engineering.Statement of significanceSelective cell retention technology (SCR) has been utilized in clinical settings to manufacture bioactive bone grafts. Specifically, demineralized bone matrix (DBM) is a widely-used SCR clinical biomaterial but it displays poor adhesion performance and angiogenic activity. In this work, we designed a collagen-binding domain (CBD) containing the core functional amino acid sequences of laminin α4 to supplement the functional surface of a collagen-based DBM scaffold. This bioscaffold promoted SCR-mediated MSCs and EPCs early cell adhesion, thus accelerated the following cell spreading, proliferation, and differentiation. Our results indicate this bioscaffold greatly induced osteogenesis and angiogenesisin vivo. In general, this bioscaffold has a good prospect for SCR application and may provide highly bioactive bone implant in clinical environment.