Enhanced endothelialization on surface modified poly(L-lactic acid) substrates.
Enhanced endothelialization on surface modified poly(L-lactic acid) substrates.
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DOI：
10.1089/ten.tea.2010.0129
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发表时间：
2010-07
影响因子：
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通讯作者：
Hao Xu;R. Deshmukh;R. Timmons;K. Nguyen
中科院分区：
文献类型：
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作者：
Hao Xu;R. Deshmukh;R. Timmons;K. Nguyen
需要改进的可生物降解的血管移植物和支架，特别是对于儿科患者。聚（L-乳酸）（PLLA）是FDA批准的可生物降解的聚合物，有可能用于此类应用。然而，组织培养研究表明，内皮细胞（EC）的附着和生长发生相对缓慢的PLLA表面。这种缓慢的生长归因于PLLA代表疏水基质，相对缺乏活性官能团的事实。因此，PLLA支架的管腔侧上的缓慢EC恢复提供了诱发血栓形成的增加的风险。在本研究中，PLLA基板的表面改性已被检查作为一个潜在的途径，以提高EC的增长。为了这个目的，PLLA表面改性通过脉冲等离子体沉积薄膜的聚（乙烯基乙酸）。通过等离子体沉积引入的-COOH表面基团被用于缀合纤连蛋白（FN），随后将血管内皮生长因子附接至FN。猪主动脉内皮细胞（PAE）和激酶插入结构域的受体（KDR）转染的PAE表现出增加的细胞粘附和增殖，以及实质上改善的细胞滞留流体剪切应力下的表面改性的PLLA相比，未经处理的PLLA。虽然KDR转染的PAE表现出更好的细胞增殖比PAE，正常的EC功能，包括EC形态，一氧化氮的生产，和KDR的表达，观察细胞生长时，表面修饰的PLLA。所获得的结果清楚地表明，这种组合的表面修饰技术，使用聚（乙烯基乙酸）沉积，FN结合，和血管内皮生长因子的表面传递可以增强对PLLA的内皮化，特别是当与KDR转染的EC的生长结合使用时。
Improved biodegradable vascular grafts and stents are in demand, particularly for pediatric patients. Poly(L-lactic acid) (PLLA) is an FDA-approved biodegradable polymer of potential use for such applications. However, tissue culture studies have shown that endothelial cell (EC) attachment and growth occurs relatively slowly on PLLA surfaces. This slow growth has been attributed to the fact that PLLA represents a hydrophobic substrate, relatively devoid of active functional groups. As a result, the slow EC recovery on the luminal side of PLLA stents provides an increased risk of induced thrombosis. In the present study, surface modification of PLLA substrates has been examined as a potential route to enhance EC growth. For this purpose, PLLA surfaces were modified via pulsed plasma deposition of thin films of poly(vinylacetic acid). The -COOH surface groups, introduced by the plasma deposition, were employed to conjugate fibronectin (FN), followed by attachment of vascular endothelial growth factor to FN. Pig Aorta ECs (PAE) and kinase-insert domain-containing receptor (KDR)-transfected PAE showed increased cell adhesion and proliferation, as well as substantially improved cell retention under fluidic shear stress on surface-modified PLLA compared with untreated PLLA. Although KDR-transfected PAE exhibited better cell proliferation than PAE, normal EC functions, including EC morphology, nitric oxide production, and KDR expression, were observed when cells were grown on surface-modified PLLA. The results obtained clearly indicate that this combined surface modification technique using poly(vinylacetic acid) deposition, FN conjugation, and vascular endothelial growth factor surface delivery can enhance endothelialization on PLLA, particularly when employed in conjunction with the growth of KDR-transfected ECs.