1 University of California Berkeley and University of California San Francisco Graduate Program in Bioengineering , San Francisco, California.
Tissue Eng Part A. 2014 Jan;20(1-2):130-8. doi: 10.1089/ten.TEA.2012.0772. Epub 2013 Sep 11.
Understanding and modulating the cellular response to implanted biomaterials is crucial for the field of tissue engineering and regenerative medicine. Since cells typically reside in an extracellular matrix containing nanoscale architecture, identifying synthetic nanostructures that induce desirable cellular behaviors could greatly impact the field. Using nanoimprint lithography, nanostructured patterns were generated on thin film polymeric materials. The ability of these surfaces to influence protein adsorption, fibroblast proliferation and morphology, and fibrotic markers was investigated. Nanostructured features with aspect ratios greater than five allowed for less protein adsorption, resulting in decreased fibroblast proliferation and rounded cellular morphology. These nanofeatures also induced significantly lower gene expression of collagen 1α2, collagen 3α1, and growth factors such as connective tissue growth factor, integrin linked kinase, transforming growth factor β1 (TGF-β1), and epidermal growth factor, key factors associated with a fibrotic response. The results demonstrate that select nanostructured surfaces could be used to modulate the fibrotic behavior in cells and have the potential to be used as antifibrotic architecture for medical implants or tissue engineering scaffolds.
理解和调节细胞对植入生物材料的反应对于组织工程和再生医学领域至关重要。由于细胞通常存在于含有纳米级结构的细胞外基质中,因此确定能诱导理想细胞行为的合成纳米结构将极大地影响该领域。本研究使用纳米压印光刻技术在薄膜聚合物材料上生成了纳米结构图案。研究了这些表面对蛋白质吸附、成纤维细胞增殖和形态以及纤维化标志物的影响。具有大于五的纵横比的纳米结构特征允许更少的蛋白质吸附,从而导致成纤维细胞增殖减少和细胞形态变圆。这些纳米特征还显著降低了胶原蛋白 1α2、胶原蛋白 3α1 和结缔组织生长因子、整合素连接激酶、转化生长因子 β1(TGF-β1)和表皮生长因子等生长因子的基因表达,这些生长因子是与纤维化反应相关的关键因素。研究结果表明,选择合适的纳米结构表面可以用来调节细胞的纤维化行为,并有可能作为医用植入物或组织工程支架的抗纤维化结构。