Laminin-111-derived peptide-hyaluronate hydrogels as a synthetic basement membrane.
Laminin-111-derived peptide-hyaluronate hydrogels as a synthetic basement membrane.
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层粘连蛋白 111 衍生的肽透明质酸水凝胶作为合成基底膜。
DOI：
10.1016/j.biomaterials.2013.05.044
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发表时间：
2013
期刊：
影响因子：
14
通讯作者：
Yuji Yamada
中科院分区：
文献类型：
--
作者：
南 晶洋;下野 洋平;Yuji Yamada
我们已经从基底膜的主要成分层粘连蛋白中鉴定出一些细胞粘附肽。来源于基底膜蛋白的细胞粘附肽是将细胞结合活性整合到组织工程支架材料中的潜在候选者。我们的目标是利用层粘连蛋白衍生的细胞粘附肽和聚合物材料开发一种化学合成的基底膜。在这项研究中，我们使用透明质酸(HA)作为支架材料，层粘连蛋白来源的细胞粘附肽A99(AGTFALRGDNPQG，与整合素αvβ3结合)，AG73(RKRLQVQLSIRT，与Syndecans结合)，以及A99/AG73混合物(摩尔比=10.9：1)连接到二维HA基质上。结果发现，2DA99/AG73-HA基质具有与基底膜提取物(BME)涂层平板相似的强大的生物学功能，如细胞附着、细胞铺展和轴突生长。接下来，我们使用A99/AG73混合物开发了三维(3D)多肽-HA骨架。3DA99/AG73-HA支架可促进细胞铺展，提高细胞存活率和胶原基因表达。此外，在3DA99/AG73-HA基质中观察到PC12突起延伸。3DA99/AG73-HA支架的这些生物学活性与3D BME支架相似。这些结果表明，多肽-HA骨架可作为二维和三维骨架，并可作为合成基底膜应用于组织工程。
We have identified a number of cell-adhesive peptides from laminins, a major component of basement membranes. Cell-adhesive peptides derived from basement membrane proteins are potential candidates for incorporating cell-binding activities into scaffold materials for tissue engineering. Our goal is development of a chemically synthetic basement membrane using laminin-derived cell-adhesive peptides and polymeric materials. In this study, we used hyaluronic acid (HA) as a scaffold material and laminin-derived cell-adhesive peptides, A99 (AGTFALRGDNPQG, binds to integrin αvβ3), AG73 (RKRLQVQLSIRT, binds to syndecans), and an A99/AG73 mixture (molar ratio = 9:1) conjugated to two-dimensional (2D) HA matrices. As a result, it was found that the 2D A99/AG73-HA matrices have strong biological functions, such as cell attachment, cell spreading, and neurite outgrowth, similar to that of basement membrane extract (BME)-coated plates. Next, we developed three-dimensional (3D) peptide-HA matrices using the A99/AG73 mixture. The 3D A99/AG73-HA matrices promoted cell spreading and improved cell viability and collagen gene expression. Further, PC12 neurite extension was observed in the 3D A99/AG73-HA matrices. These biological activities of the 3D A99/AG73-HA matrices were similar to those of the 3D BME matrices. These results suggest that the peptide-HA matrices are useful as 2D and 3D matrices and can be applied for tissue engineering as a synthetic basement membrane.