Carpenter Joseph, Khang Dongwoo, Webster Thomas J
Division of Engineering, Brown University, Providence, RI 02912, USA.
Nanotechnology. 2008 Dec 17;19(50):505103. doi: 10.1088/0957-4484/19/50/505103. Epub 2008 Nov 24.
Current small diameter (<5 mm) synthetic vascular graft materials exhibit poor long-term patency due to thrombosis and intimal hyperplasia. Tissue engineered solutions have yielded functional vascular tissue, but some require an eight-week in vitro culture period prior to implantation-too long for immediate clinical bedside applications. Previous in vitro studies have shown that nanostructured poly(lactic-co-glycolic acid) (PLGA) surfaces elevated endothelial cell adhesion, proliferation, and extracellular matrix synthesis when compared to nanosmooth surfaces. Nonetheless, these studies failed to address the importance of lateral and vertical surface feature dimensionality coupled with surface free energy; nor did such studies elicit an optimum specific surface feature size for promoting endothelial cell adhesion. In this study, a series of highly ordered nanometer to submicron structured PLGA surfaces of identical chemistry were created using a technique employing polystyrene nanobeads and poly(dimethylsiloxane) (PDMS) molds. Results demonstrated increased endothelial cell adhesion on PLGA surfaces with vertical surface features of size less than 18.87 nm but greater than 0 nm due to increased surface energy and subsequently protein (fibronectin and collagen type IV) adsorption. Furthermore, this study provided evidence that the vertical dimension of nanometer surface features, rather than the lateral dimension, is largely responsible for these increases. In this manner, this study provides key design parameters that may promote vascular graft efficacy.
当前的小直径(<5毫米)合成血管移植材料由于血栓形成和内膜增生,长期通畅性较差。组织工程解决方案已产生功能性血管组织,但有些在植入前需要八周的体外培养期,这对于即时临床床边应用来说太长了。先前的体外研究表明,与纳米光滑表面相比,纳米结构的聚乳酸-乙醇酸共聚物(PLGA)表面能提高内皮细胞的粘附、增殖和细胞外基质合成。然而,这些研究没有解决横向和垂直表面特征维度与表面自由能的重要性;此类研究也没有得出促进内皮细胞粘附的最佳特定表面特征尺寸。在本研究中,使用一种采用聚苯乙烯纳米珠和聚二甲基硅氧烷(PDMS)模具的技术,制备了一系列化学性质相同的高度有序的纳米至亚微米结构的PLGA表面。结果表明,由于表面能增加以及随后蛋白质(纤连蛋白和IV型胶原)吸附增加,在尺寸小于18.87纳米但大于0纳米的具有垂直表面特征的PLGA表面上,内皮细胞粘附增加。此外,本研究提供的证据表明,纳米表面特征的垂直维度而非横向维度在很大程度上导致了这些增加。通过这种方式,本研究提供了可能促进血管移植功效的关键设计参数。