Miller Derick C, Thapa Anil, Haberstroh Karen M, Webster Thomas J
Department of Biomedical Engineering, Purdue University, West Lafayette, IN 47907-1296, USA.
Biomaterials. 2004 Jan;25(1):53-61. doi: 10.1016/s0142-9612(03)00471-x.
Biomaterials that successfully integrate into surrounding tissue should match not only the tissue's mechanical properties, but also its topography. The cellular response to a biomaterial may be enhanced in synthetic polymer formulations by mimicking the surface roughness created by the associated nano-structured extra-cellular matrix components of natural tissue. As a first step towards this endeavor, the goal of the present in vitro study was to use these design parameters to develop a synthetic, nano-structured, polymeric biomaterial that promotes cell adhesion and growth for vascular applications. In a novel manner, poly(lactic-co-glycolic acid) (PLGA) (50/50wt% mix) was synthesized to possess a range (from micron to nanometer) of surface features. Reduction of surface features was accomplished by treating conventional PLGA with various concentrations of NaOH for select periods of time. Results from cell experiments indicated that, compared to conventional PLGA, NaOH treated PLGA enhanced vascular smooth muscle cell adhesion and proliferation. However, PLGA prepared by soaking in NaOH decreased endothelial cell adhesion and proliferation compared to conventional PLGA. After further investigation, this finding was determined to be a result of chemical (and not topographical) changes during polymer synthesis. Surface chemistry effects were removed while retaining nano-structured topography by using polymer/elastomer casting methods. Results demonstrated that endothelial and smooth muscle cell densities increased on nano-structured cast PLGA. For these reasons, the present in vitro study provided the first evidence that nano-structured surface features can significantly improve vascular cell densities; such design criteria can be used in the synthesis of the next-generation of more successful tissue-engineered vascular grafts.
能够成功整合到周围组织中的生物材料不仅应匹配组织的机械性能，还应匹配其拓扑结构。通过模仿天然组织相关纳米结构细胞外基质成分所产生的表面粗糙度，合成聚合物配方中生物材料的细胞反应可能会增强。作为朝着这一目标迈出的第一步，本体外研究的目的是利用这些设计参数开发一种合成的、纳米结构的聚合物生物材料，以促进血管应用中的细胞粘附和生长。以一种新颖的方式，合成了聚乳酸-乙醇酸共聚物（PLGA）（50/50重量%混合物），使其具有一系列（从微米到纳米）的表面特征。通过在选定的时间段内用不同浓度的NaOH处理传统PLGA来实现表面特征的减少。细胞实验结果表明，与传统PLGA相比，经NaOH处理的PLGA增强了血管平滑肌细胞的粘附和增殖。然而，与传统PLGA相比，通过浸泡在NaOH中制备的PLGA降低了内皮细胞的粘附和增殖。经过进一步研究，这一发现被确定为聚合物合成过程中化学（而非拓扑）变化的结果。通过使用聚合物/弹性体浇铸方法，在保留纳米结构拓扑的同时消除了表面化学效应。结果表明，纳米结构浇铸PLGA上的内皮细胞和平滑肌细胞密度增加。基于这些原因，本体外研究提供了首个证据，即纳米结构表面特征可显著提高血管细胞密度；此类设计标准可用于合成下一代更成功的组织工程血管移植物。
