Multiple integrin ligands provide a highly adhesive and osteoinductive surface that improves selective cell retention technology
Multiple integrin ligands provide a highly adhesive and osteoinductive surface that improves selective cell retention technology
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多个整合素配体提供了高度粘附和骨诱导的表面，改善了选择性细胞保留技术。
DOI：
10.1016/j.actbio.2018.12.018
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发表时间：
2019-02-01
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：
Luo, Keyu;Gao, Xiaoliang;Luo, Fei
在各种骨组织工程策略中，选择性细胞保留（SCR）技术已被用作真实的实时制造骨移植物的实用临床方法。保留的间充质干细胞（MSC）越多，支架提供的骨诱导微环境就越好，这反过来又促进了SCR制造的骨移植物的成骨。整合素受体对细胞-基质粘附和信号转导至关重要。我们设计了一种含有胶原结合结构域（CBD）的IKVAV-cRGD肽（CBD-IKVAV-cRGD肽），以补充具有含有多种整合素配体的功能化表面的胶原基脱矿骨基质（DBM），这些配体对应于MSC上高度表达的整合素亚型。该DBM/CBD-IKVAV-cRGD复合物表现出对培养的MSC的上级体外粘附能力，如通过振荡细胞粘附测定、离心细胞粘附测定和模拟SCR所确定的。在临床SCR法中，其可促进MSC样CD 271（+）细胞和MSC样CD 90（+）/CD 105（+）细胞的保留。此外，DBM/CBD-IKVAV-cRGD复合物诱导了稳健的MSC成骨，同时激活了整合素的下游FAK-ERK 1/2信号通路。SCR制备的DBM/CBD-IKVAV-cRGD复合材料在体内表现出良好的上级成骨能力，表明其可能作为生物材料用于SCR介导的骨移植。具体而言，脱矿骨基质（DBM）是一种广泛使用的SCR临床生物材料，但其表现出较差的粘附性能和骨诱导。促进细胞粘附和骨诱导的DBM的改进将有益于SCR制备的植入物。在这项工作中，我们开发了一种新的肽，补充DBM与功能化的表面的多个整合素配体，这是对应于整合素亚型上的人骨髓来源的间充质干细胞（MSC）。我们的研究结果表明，这种新的功能化生物支架大大增加了SCR介导的MSC粘附和体内成骨。总的来说，这种新型材料具有很好的SCR应用前景，可能在临床环境中提供高生物活性骨植入物。(C)2018 Acta Materialia Inc.由爱思唯尔有限公司出版。保留所有权利。
Among various bone tissue engineering strategies, selective cell retention (SCR) technology has been used as a practical clinical method for bone graft manufacturing in real time. The more mesenchymal stem cells (MSCs) are retained, the better the osteoinductive microenvironment provided by the scaffold, which in turn promotes the osteogenesis of the SCR-fabricated bone grafts. Integrin receptors are crucial to cell-matrix adhesion and signal transduction. We designed a collagen-binding domain (CBD)-containing IKVAV-cRGD peptide (CBD-IKVAV-cRGD peptide) to complement the collagen-based demineralized bone matrix (DBM) with a functionalized surface containing multiple integrin ligands, which correspond to the highly expressed integrin subtypes on MSCs. This DBM/CBD-IKVAV-cRGD composite exhibited superior in vitro adhesion capacity to cultured MSCs, as determined by oscillatory cell adhesion assay, centrifugal cell adhesion assay and mimetic SCR. Moreover, it promoted the retention of MSC-like CD271(+) cells and MSC-like CD90(+)/CD105(+) cells in the clinical SCR method. Furthermore, the DBM/CBD-IKVAV-cRGD composite induced robust MSC osteogenesis, coupled with the activation of the downstream FAK-ERK1/2 signaling pathway of integrins. The SCR-prepared DBM/CBD-IKVAV-cRGD composite displayed superior in vivo osteogenesis, indicating that it may be potentially utilized as a biomaterial in SCR-mediated bone transplantation.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 osteoinduction. Improvements of the DBM that promote cell adhesion and osteoinduction will benefit SCR-prepared implants. In this work, we developed a novel peptide that complements the DBM with a functionalized surface of multiple integrin ligands, which are corresponding to integrin subtypes available on human bone marrow-derived mesenchymal stem cells (MSCs). Our results indicate this novel functionalized bioscaffold greatly increases SCR-mediated MSC adhesion and in vivo osteogenesis. Overall, this novel material has promising SCR applications and may likely provide highly bioactive bone implants in clinical settings. (C) 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.