School of Chemical & Biomolecular Engineering, Georgia Institute of Technology, 311 Ferst Drive NW, Atlanta, Georgia 30332-0100, USA.
Biomacromolecules. 2012 May 14;13(5):1420-8. doi: 10.1021/bm300144y. Epub 2012 Apr 6.
Engineering materials suitable for vascular prostheses has been a significant challenge, especially in promoting extracellular matrix (ECM) development within synthetic materials. Herein we have utilized two different elastin mimetic peptide sequences, EM-19 and EM-23, to provide a template for ECM deposition when covalently incorporated into scaffold materials. Both peptides contain the hexapeptide sequence VGVAPG, which interacts with the cell surface receptor known as the elastin binding protein (EBP). Additionally, EM-23 contains an RGDS sequence intended for the peptide's interaction with the α(v)β(3) integrin. We first confirm that the presence of both peptides approximates the synergistic mechanism for elastic fiber assembly in vivo, a process that utilizes both the EBP and α(v)β(3). Peptides were then grafted onto the surface of a poly(ethylene glycol) diacrylate (PEG-DA) hydrogel and their efficacy as templates for promoting cell adhesion, spreading, and elastin deposition was evaluated. Although both peptides were able to encourage smooth muscle cell (SMC) adhesion and elastin deposition over PEG-DA and PEG-RGDS controls, PEG-grafted EM-23 was proven to be the more promising motif for inclusion in synthetic substrates to be used in the engineering of vascular tissues, enhancing cell adhesion 60-fold and elastin content 2-fold compared with PEG-RGDS.
用于血管假体的工程材料一直是一个重大挑战,特别是在促进合成材料内细胞外基质 (ECM) 的发展方面。在此,我们利用两种不同的弹性蛋白模拟肽序列 EM-19 和 EM-23,当共价结合到支架材料中时,为 ECM 沉积提供模板。这两种肽都包含六肽序列 VGVAPG,它与细胞表面受体即弹性蛋白结合蛋白 (EBP) 相互作用。此外,EM-23 包含一个 RGDS 序列,用于肽与α(v)β(3)整联蛋白的相互作用。我们首先证实,这两种肽的存在接近体内弹性纤维组装的协同机制,这一过程同时利用 EBP 和α(v)β(3)。然后将肽接枝到聚乙二醇二丙烯酸酯 (PEG-DA) 水凝胶的表面,并评估它们作为促进细胞黏附、铺展和弹性蛋白沉积模板的功效。虽然两种肽都能够促进平滑肌细胞 (SMC) 在 PEG-DA 和 PEG-RGDS 对照物上的黏附和弹性蛋白沉积,但已证明 PEG 接枝的 EM-23 更适合包含在用于血管组织工程的合成基质中,与 PEG-RGDS 相比,它将细胞黏附提高了 60 倍,弹性蛋白含量提高了 2 倍。