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Synthesis and Evaluation of Peptide-based Hybrid Scaffold for Tissue Engineering

组织工程用肽混合支架的合成与评价

基本信息

批准号：
17500320
负责人：
HIRANO Yoshiaki
金额：
$ 2.18万
依托单位：
Osaka Institute of Technology
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

项目摘要

In tissue engineering and wound-healing application, scaffold materials are utilized to provide a mechanical support for cell growth and tissue formation. These scaffold can be modified such that they also provide specific biologic signals to cell in order to control or facilitate tissue formation or regeneration. Cell adhesion peptides Arg-Gly-Asp (RGD) have been incorporated into scaffolds to enhance cell adhesion or to allow biospecific cell adhesion.In this work, for improving the cell-attachment activity of the Arg-Gly-Asp-Ser peptides to tissue engineering scaffold, we tried to stabilize the folded conformations of such peptides by designing the ss-strands peptides, which have the Arg-Gly-Asp-Ser sequence at the C-terminal. These sequence, (Ala-Glu-Ala-Glu-Ala-Lys-Ala-Lys)_2 (EAK16) or (Arg-Ala-Arg-Ala-Asp-Ala-Asp-Ala)_2 (RAD16) of the peptides is selected as a typical sequence for having high propensity to form ss-strands.RGDS containing ss-strands model peptides were synthesize … More d using liquid and solid phase procedures. Fibroblast cells attaching to the peptide-immobilized cell culture dishes, indicating that difference in the cell-attachment activity were found for these peptides-immobilized cell culture dishes. EAK16RGDS and RAD16RGDS immobilized polystyrene-dish has the highest spreading activity among the peptide-immobilized ones.The conformational constraint caused by the formation of ss-strands structure is too strong to stabilize the desired conformation at the Arg-Gly-Asp-Ser portion for the peptides in which the Arg-Gly-Asp-Ser sequence is directly linked to the sequences designed for forming ss-strands structure. It is also suggested that designing a spacer sequence is desirable for improving the activity between the Arg-Gly-Asp-Ser sequence and the sequence forming ss-strand structure. Solutions of EAK16RGDS and RAD16RGDS become gelatinous and then form fibers. EAK16RGDS and RAD16RGDS peptides interact with each other and become more structured upon fiber formation. Such peptides may find utility as in vivo tissue engineering 3D scaffolds. Less

在组织工程和伤口愈合应用中，支架材料用于为细胞生长和组织形成提供机械支撑。这些支架可以被修饰，使得它们还向细胞提供特定的生物信号，以控制或促进组织形成或再生。细胞粘附肽Arg-Gly-Asp (RGD)已被纳入支架中以增强细胞粘附或允许生物特异性细胞粘附。在这项工作中，为了提高Arg-Gly-Asp-Ser肽对组织工程支架的细胞粘附活性，我们尝试通过设计单链肽来稳定此类肽的折叠构象，其具有 C 端的 Arg-Gly-Asp-Ser 序列。选择肽的这些序列（Ala-Glu-Ala-Glu-Ala-Lys-Ala-Lys）_2（EAK16）或（Arg-Ala-Arg-Ala-Asp-Ala-Asp-Ala）_2（RAD16）作为具有高形成单链倾向的典型序列。合成了含有单链模型肽的RGDS……更多d 使用液相和固相程序。成纤维细胞附着在肽固定的细胞培养皿上，表明这些肽固定的细胞培养皿的细胞附着活性存在差异。 EAK16RGDS和RAD16RGDS固定化聚苯乙烯平皿在肽固定化平皿中具有最高的铺展活性。对于其中Arg-Gly-Asp-Ser序列直接连接到设计用于形成的序列的肽，由形成单链结构引起的构象限制太强，无法稳定Arg-Gly-Asp-Ser部分的所需构象。 SS-链结构。还建议设计间隔序列对于提高Arg-Gly-Asp-Ser序列和形成单链结构的序列之间的活性是理想的。 EAK16RGDS和RAD16RGDS的溶液变成凝胶状，然后形成纤维。 EAK16RGDS 和 RAD16RGDS 肽彼此相互作用，并在纤维形成时变得更加结构化。此类肽可用作体内组织工程 3D 支架。较少的