A novel injectable peptide-based hydrogel for myocardial infarction treatment

一种用于心肌梗塞治疗的新型可注射肽基水凝胶

• 批准号: 22659236
• 负责人: NAKATANI Takeshi
• 金额: $ 2.12万
• 依托单位: National Cardiovascular Center Research Institute
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22659236/
• 关键词: 人工臓器学; 心筋梗塞; ゲル注入療法; ペプチドゲル; 組織リモデリング; βターン; 生分解性

Recently, injection of bio-derived hydrogels into myocardial infarction have been investigated for the novel treatment for left ventricular remodeling. In this study, a novel thermoresponsive peptide-type injectable gel matrix composed of naturally occurring sequences were developed, and their therapeutic efficiency was evaluated. A small peptide, Ac-(RVEIKVDI) 2-CONH2 which mimics an anti-parallelβ-sheet region ofβ2-microblobulin, forms hydrogel in situ with high water content in 10v% DMSO aqueous solution. Its solution formed hydrogel in approximately 3 minutes at room temperature. Hydrogelation of the peptide solution is driven by electrostatic and hydrophobic interaction with the conformational change from random coil toβ-sheet structure, as assumed from FT-IR measurement. This hydrogel is rigid(G'> 300 Pa) and is not disrupted in PBS for over 24 hours. In addition, the peptide solution is easily injected into the body by syringe with thin needle, and the resultant hydrogel did not result in serve inflammation. This peptide hydrogel may have implication for in situ forming biomaterials. In addition, we confirmed that the injection of biodegradable hydrogel into the myocardial infarction is as effective as the previous non-degradable one may be via a different mechanism.

最近，将生物衍生的水凝胶注射到心肌梗死中已被研究用于左心室重构的新治疗。在这项研究中，开发了一种新的由天然序列组成的温度响应肽型可注射凝胶基质，并对其治疗效率进行了评价。一种模拟β2-微球蛋白的反平行β折叠区的小肽Ac-（RVEIKO）2-CONH 2在10v%DMSO水溶液中原位形成具有高含水量的水凝胶。其溶液在室温下在约3分钟内形成水凝胶。肽溶液的水凝胶化由静电和疏水相互作用驱动，构象从无规卷曲变为β-折叠结构，如FT-IR测量所假设的。该水凝胶是刚性的（G '> 300 Pa），并且在PBS中超过24小时不被破坏。此外，肽溶液易于通过具有细针的注射器注射到体内，并且所得水凝胶不会导致严重炎症。这种肽水凝胶可能具有原位形成生物材料的意义。此外，我们证实，可生物降解的水凝胶注射到心肌梗死是有效的，因为以前的不可降解的一个可能是通过不同的机制。

项目成果

生体親和性ペプチドハイドロゲルの徐放型アンチセンス療法への展開

将生物相容性肽水凝胶开发成缓释反义疗法

• 发表时间: 2011
• 作者: 宇都宮徹;ほか(11人中3番目);鳥越俊彦;柿木佐知朗
• 通讯作者: 柿木佐知朗

Global gene expression analysis of biological responses for porous polymer scaffolds with different molecular architecture

不同分子结构多孔聚合物支架生物反应的全局基因表达分析

• 发表时间: 2011
• 作者: K.Saito;et al.;Tokura Y;柿木佐知朗
• 通讯作者: 柿木佐知朗

心臓移植

心脏移植

• 发表时间: 2011
• 作者: Sakata R;Fujii Y;Kuwano H;松田暉
• 通讯作者: 松田暉

Platelet response to PEG-modified surface with different molecular architecture

血小板对具有不同分子结构的 PEG 修饰表面的反应

• 发表时间: 2011
• 作者: Tsuruma. T;et al.;柿木佐知朗
• 通讯作者: 柿木佐知朗

多孔質スキャホールドの移植が引起す炎症反応の遺伝子チップを用いた網羅解析

利用基因芯片综合分析多孔支架移植引起的炎症反应

• 发表时间: 2011
• 作者: Maeda S;Motoi F;Onogawa T;et al;柿木佐知朗
• 通讯作者: 柿木佐知朗