Meredith J Carson, Sormana Joe-L, Keselowsky Benjamin G, García Andrés J, Tona Alessandro, Karim Alamgir, Amis Eric J
School of Chemical Engineering, Georgia Institute of Technology, 311 Ferst Dr., Atlanta, Georgia 30332-0100, USA.
J Biomed Mater Res A. 2003 Sep 1;66(3):483-90. doi: 10.1002/jbm.a.10004.
We report a novel combinatorial methodology for characterizing the effects of polymer surface features on cell function. Libraries containing hundreds to thousands of distinct chemistries, microstructures, and roughnesses are prepared using composition spread and temperature gradient techniques. The method enables orders of magnitude increases in discovery rate, decreases variance, and allows for the first time high-throughput assays of cell response to physical and chemical surface features. The technique overcomes complex variable spaces that limit development of biomaterial surfaces for control of cell function. This report demonstrates these advantages by investigating the sensitivity of osteoblasts to the chemistry, microstructure, and roughness of poly(D,L-lactide) and poly(epsilon-caprolactone) blends. In particular, we use the phenomenon of heat-induced phase separation in these polymer mixtures to generate libraries with diverse surface features, followed by culture of UMR-106 and MC3T3-E1 osteoblasts on the libraries. Surface features produced at a specific composition and process temperature range were discovered to enhance dramatically alkaline phosphatase expression in both cell lines, not previously observed for osteoblasts on polymer blends.
我们报告了一种用于表征聚合物表面特征对细胞功能影响的新型组合方法。使用成分扩展和温度梯度技术制备包含数百至数千种不同化学组成、微观结构和粗糙度的文库。该方法使发现率提高了几个数量级,降低了方差,并首次实现了对细胞对物理和化学表面特征反应的高通量检测。该技术克服了限制用于控制细胞功能的生物材料表面发展的复杂变量空间。本报告通过研究成骨细胞对聚(D,L-丙交酯)和聚(ε-己内酯)共混物的化学组成、微观结构和粗糙度的敏感性来证明这些优势。特别是,我们利用这些聚合物混合物中的热致相分离现象来生成具有不同表面特征的文库,然后在文库上培养UMR-106和MC3T3-E1成骨细胞。发现在特定组成和工艺温度范围内产生的表面特征能显著增强两种细胞系中的碱性磷酸酶表达,这在之前聚合物共混物上的成骨细胞中未曾观察到。