Department of Biomedical Engineering, Saint Louis University, Saint Louis, Missouri, USA.
J Biomed Mater Res A. 2010 Jun 1;93(3):817-23. doi: 10.1002/jbm.a.32775.
Over the past decade, it has been increasingly recognized that both chemical and mechanical properties of scaffolds influence neural cell behavior, ranging from growth to differentiation to migration. However, mechanical properties are difficult to control for in the design of scaffolds for nerve regeneration, as properties change over time for most biologically derived scaffolds. The focus of this project was to examine how the mechanical properties of a nondegradable scaffold, poly(ethylene glycol) (PEG) gels, influenced nerve cell behavior. Low concentration PEG gels, of 3, 4, or 5% PEG, with added collagen to alter chemical properties were examined for both their mechanical properties and their ability to support nerve expression and extension. Stiffness (G*) significantly increased with increased PEG concentration. The addition of chemically conjugated collagen significantly decreased the stiffness compared to plain gels. This phenomenon was confirmed to be an effect of the conjugate, and not the protein itself, as G* of gels containing conjugate, but no protein, was not significantly different than G* of gels with conjugated protein. PC12 cell neurite expression increased with decreasing PEG and increasing collagen concentration. At its best, the expression approached the value on collagen-coated tissue culture plastic, which is a substantial improvement over previous studies on PEG. Neurite extension of dorsal root ganglia was also improved on these same gels over gels with either higher PEG concentration or lower collagen amount. Overall, these results suggest that exploration of lower stiffness materials is necessary to improve neurite growth and extension in three-dimensional synthetic scaffolds.
在过去的十年中，人们越来越认识到支架的化学和机械性能都会影响神经细胞的行为，从生长到分化再到迁移。然而，在神经再生支架的设计中，很难控制机械性能，因为大多数生物衍生支架的性能会随时间而改变。本项目的重点是研究不可降解支架聚乙二醇（PEG）凝胶的机械性能如何影响神经细胞的行为。研究了具有不同化学性质的低浓度（3%、4%或 5%PEG）和添加胶原改变化学性质的 PEG 凝胶的机械性能及其支持神经表达和延伸的能力。PEG 浓度增加，凝胶的硬度（G*）显著增加。与纯凝胶相比，化学偶联胶原的添加显著降低了硬度。这一现象被证实是偶联物的作用，而不是蛋白质本身的作用，因为含有偶联物但不含蛋白质的凝胶的 G与含有共轭蛋白质的凝胶的 G没有显著差异。PC12 细胞的神经突表达随 PEG 浓度降低和胶原浓度增加而增加。在最佳状态下，其表达接近涂有胶原蛋白的组织培养塑料上的表达值，这比以前关于 PEG 的研究有了很大的提高。在相同的凝胶上，背根神经节的神经突延伸也比具有较高 PEG 浓度或较低胶原量的凝胶有所改善。总的来说，这些结果表明，有必要探索更低刚度的材料，以改善三维合成支架中的神经突生长和延伸。
