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肝素模拟肽纳米纤维促进血管生成。

Heparin mimetic peptide nanofibers promote angiogenesis.

机构信息

UNAM-Institute of Materials Science and Nanotechnology, Bilkent University, Ankara 06800, Turkey.

出版信息

Biomacromolecules. 2011 Oct 10;12(10):3508-19. doi: 10.1021/bm200957s. Epub 2011 Sep 7.

Abstract

New blood vessel formation (angiogenesis) is one of the most important processes required for functional tissue formation. Induction of angiogenesis is usually triggered by growth factors released by cells. Glycosaminoglycans (e.g., heparan sulphates) in the extracellular matrix aid in proper functioning of these growth factors. Therefore, exogeneous heparin or growth factors were required for promoting angiogenesis in previous regenerative medicine studies. Here we report for the first time induction of angiogenesis by a synthetic nanofibrous peptide scaffold without the addition of any exogenous growth factors or heparin. We designed and synthesized a self-assembling peptide amphiphile molecule that is functionalized with biologically active groups to mimic heparin. Like heparin, this molecule has the ability to interact with growth factors and effectively enhance their bioactivity. The nanofibers formed by these molecules were shown to form a 3D network mimicking the structural proteins in the extracellular matrix. Because of heparin mimicking capabilities of the peptide nanofibers, angiogenesis was induced without the addition of exogenous growth factors in vitro. Bioactive interactions between the nanofibers and the growth factors enabled robust vascularization in vivo as well. Heparin mimetic peptide nanofibers presented here provide new opportunities for angiogenesis and tissue regeneration by avoiding the use of heparin and exogenous growth factors. The synthetic peptide nanofiber scaffolds enriched with proper chemical functional groups shown in this study can be used to induce various desired physiological responses for tissue regeneration.

摘要

新血管形成(血管生成)是功能性组织形成所必需的最重要过程之一。血管生成的诱导通常是由细胞释放的生长因子触发的。细胞外基质中的糖胺聚糖(例如,硫酸乙酰肝素)有助于这些生长因子的正常功能。因此,在以前的再生医学研究中,需要外源性肝素或生长因子来促进血管生成。在这里,我们首次报道了在没有添加任何外源性生长因子或肝素的情况下,通过合成的纳米纤维肽支架诱导血管生成。我们设计并合成了一种自组装的肽两亲分子,其功能化有生物活性基团以模拟肝素。与肝素一样,这种分子具有与生长因子相互作用并有效增强其生物活性的能力。这些分子形成的纳米纤维形成了类似于细胞外基质中结构蛋白的 3D 网络。由于肽纳米纤维具有模拟肝素的能力,因此无需添加外源性生长因子即可在体外诱导血管生成。纳米纤维与生长因子之间的生物活性相互作用也能够在体内实现强大的血管化。本文介绍的肝素模拟肽纳米纤维为避免使用肝素和外源性生长因子促进血管生成和组织再生提供了新的机会。本研究中所示的富含适当化学官能团的合成肽纳米纤维支架可用于诱导组织再生所需的各种生理反应。

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