Growth Factor-Bearing Polymer Brushes--Versatile Bioactive Substrates Influencing Cell Response.
Growth Factor-Bearing Polymer Brushes--Versatile Bioactive Substrates Influencing Cell Response.
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DOI：
10.1021/acs.biomac.5b00967
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发表时间：
2015-10
影响因子：
6.2
通讯作者：
Evmorfia Psarra;E. Foster;U. König;Jungmok You;Y. Ueda;K. Eichhorn;M. Müller;M. Stamm;A. Revzin;P. Uhlmann
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文献类型：
--
作者：
Evmorfia Psarra;E. Foster;U. König;Jungmok You;Y. Ueda;K. Eichhorn;M. Müller;M. Stamm;A. Revzin;P. Uhlmann
在这项研究中，我们介绍了基于整合的生物活性信号线索而开发的具有细胞导向特性的响应性纳米级底物。研究方法考虑了两种不同的表面结合生长因子(GFS)对细胞行为和反应的影响：肝细胞生长因子(HGF)和碱性成纤维细胞生长因子(BFGF)。探索了两种表面生物功能化策略，以构思多功能、生物活性的聚合物刷膜。采用物理吸附和化学吸附两种方法，对高分子链接枝率较高的聚丙烯酸(PAA)聚合物层进行生物功能化处理。基于它们的初始负载浓度，两种GF对PAA刷子都显示出很高的结合效率。根据所应用的生物功能化方法，可以区分GF的释放动力学。具体地说，在物理吸附的HGF和bFGF的情况下，都观察到了高的初始猝发之后持续的缓慢释放。相比之下，化学吸附的GFS的释放动力学有很大的不同。值得注意的是，化学吸附的HGF结合在刷面上的时间长达1周以上，而50%的化学吸附的bFGF释放缓慢。此外，还研究了这些GF生物功能化PAA刷子对不同细胞的影响。以人肝癌细胞株(HepG2)为研究对象，通过细胞生长抑制实验和散射实验，分析了HGF修饰PAA刷剂的生物活性。此外，还研究了小鼠胚胎干细胞在碱性成纤维细胞生长因子修饰的PAA刷子表面向内胚层分化的情况。最后，结果表明，PAA刷子，特别是那些用化学吸附的GFS进行生物功能化的刷子，对这两种类型的细胞都产生了预期的可测量的影响。因此，经GFS生物功能化的PAA聚合物刷可以作为生物活性细胞培养基质，具有良好的调谐效率。
In this study we present the development of responsive nanoscale substrates exhibiting cell-guiding properties based on incorporated bioactive signaling cues. The investigative approach considered the effect of two different surface-bound growth factors (GFs) on cell behavior and response: hepatocyte growth factor (HGF) and basic fibroblast growth factor (bFGF). Two surface biofunctionalization strategies were explored in order to conceive versatile, bioactive thin polymer brush films. Polymer brushes made of tethered poly(acrylic)acid (PAA) polymer layers with a high grafting density of polymer chains were biofunctionalized with GFs either by physisorption or chemisorption. Both GFs showed high binding efficiencies to PAA brushes based on their initial loading concentrations. The GF release kinetics can be distinguished depending on the applied biofunctionalization method. Specifically, a high initial burst followed by a constant slow release was observed in the case of both physisorbed HGF and bFGF. In contrast, the release kinetics of chemisorbed GFs were quite different. Remarkably, chemisorbed HGF remained bound to the brush surface for over 1 week, whereas 50% of chemisorbed bFGF was released slowly. Furthermore, the effect of these GF-biofunctionalized PAA brushes on different cells was investigated. A human hepatoma cell line (HepG2) was used to analyze the bioactivity of HGF-modified PAA brushes by measuring cell growth inhibition and scattering effects. Additionally, the differentiation of mouse embryonic stem cells (mESCs) toward endoderm was studied on bFGF-modified PAA brush surfaces. Finally, the results illustrate that PAA brushes, particularly those biofunctionalized with chemisorbed GFs, produce an expected measurable effect on both cell types. Therefore, PAA polymer brushes biofunctionalized with GFs can be used as bioactive cell culture substrates with tuned efficiency.