Laminin alpha 4 promotes bone regeneration by facilitating cell adhesion and vascularization

间充质干细胞 细胞生物学 川地31 内皮祖细胞 细胞外基质 祖细胞 细胞粘附 脚手架 粘附 整合素 脱钙骨基质 化学 血管生成 干细胞 材料科学 生物医学工程 细胞 数据库管理 癌症研究 生物 医学 生物化学 复合材料 放大器 光电子学 CMOS芯片
作者
Yong Tang,Keyu Luo,Jiulin Tan,Rui Zhou,Yueqi Chen,Can Chen,Zhigang Rong,Min‐Zhi Deng,Xueke Yu,Chengmin Zhang,Qijie Dai,Wenjie Wu,Jianzhong Xu,Shiwu Dong,Fei Luo
出处
期刊:Acta Biomaterialia [Elsevier]
卷期号:126: 183-198 被引量:12
标识
DOI:10.1016/j.actbio.2021.03.011
摘要

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 angiogenesis in vivo, suggesting that it might be used as a new biomaterial in bone tissue engineering. STATEMENT OF SIGNIFICANCE: Selective 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 angiogenesis in vivo. In general, this bioscaffold has a good prospect for SCR application and may provide highly bioactive bone implant in clinical environment.
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