Designing scaffolds for valvular interstitial cells: Cell adhesion and function on naturally derived materials

Designing scaffolds for valvular interstitial cells: Cell adhesion and function on naturally derived materials
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DOI:
10.1002/jbm.a.30149
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发表时间:
2004-10-01
影响因子:
4.9
通讯作者:
Anseth, KS
Anseth, KS
中科院分区:
工程技术3区
文献类型:
--
作者:
Masters, KS;Shah, DN;Anseth, KS

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瓣膜间质细胞(VICs)具有许多特性,使其在构建组织工程瓣膜方面具有吸引力;然而,我们发现VICs附着和扩散的表面是有限的。例如,VIC在胶原和层粘连蛋白涂层的表面上附着和扩散,但显示出改变的形态,不会增殖。有趣的是,纤维连接蛋白(FN)是一种促进VIC黏附和增殖的黏附蛋白。然而,VIC不会在RGD修饰的表面上扩散,RGD是一种普遍存在的细胞粘附肽,也不会与其他FN特异的肽序列如EILDV和PHSRN一起修饰。透明质酸(HA)是一种高弹性的多糖,参与了天然瓣膜的形态发生,并与FN具有结合作用。将透明质酸修饰成可光聚合的水凝胶,发现VICs在HA基凝胶上扩散和增殖,在4d内在凝胶上形成融合的单分子层。修饰后的HA保留了其与FN特异性结合的能力,允许形成同时包含HA和FN的凝胶。培养在HA表面的瓣膜间质细胞明显增加细胞外基质蛋白的产生,提示HA支架可能为刺激心脏瓣膜组织的形成提供有用的生物学线索。(C)2004年威利期刊公司。
Valvular interstitial cells (VICs) possess many properties that make them attractive for use in the construction of a tissue-engineered valve; however, we have found that the surfaces to which VICs will adhere and spread are limited. For example, VICs adhere and spread on collagen and laminin-coated surfaces, but display altered morphology and do not proliferate. Interestingly, fibronectin (FN) was one adhesion protein that facilitated VIC adhesion and proliferation. Yet VICs did not spread on surfaces modified with RGD, a ubiquitous cell-adhesive peptide, nor with other FN-specific peptide sequences such as EILDV and PHSRN. Hyaluronic acid (HA) is a highly elastic polysaccharide that is involved in natural valve morphogenesis and possesses binding interactions with FN. Hyaluronic acid was modified to form photopolymerizable hydrogels, and VICs were found to spread and proliferate on HA-based gels, forming a confluent monolayer on the gels within 4 days. Modified HA retained its ability to specifically bind FN, allowing for the formation of gels containing both HA and FN. Valvular interstital cells cultured on HA surfaces displayed significantly increased production of extracellular matrix proteins, indicating that HA-based scaffolds may provide useful biological cues to stimulate heart valve tissue formation. (C) 2004 Wiley Periodicals, Inc.