State Key Laboratory of Molecular Engineering of Polymers, Collaborative Innovation Center of Polymers and Polymer Composite Materials, Department of Macromolecular Science, Advanced Materials Laboratory, Fudan University , Shanghai 200433, China.
Nano Lett. 2015 Nov 11;15(11):7755-65. doi: 10.1021/acs.nanolett.5b04043. Epub 2015 Oct 28.
Cell dedifferentiation is of much importance in many cases such as the classic problem of dedifferentiation of chondrocytes during in vitro culture in cartilage tissue engineering. While cell differentiation has been much investigated, studies of cell dedifferentiation are limited, and the nanocues of cell dedifferentiation have little been reported. Herein, we prepared nanopatterns and micro/nanopatterns of cell-adhesive arginine-glycine-aspartate (RGD) peptides on nonfouling poly(ethylene glycol) (PEG) hydrogels to examine the effects of RGD nanospacing on adhesion and dedifferentiation of chondrocytes. The relatively larger RGD nanospacing above 70 nm was found to enhance the maintainence of the chondrocyte phenotype in two-dimensional culture, albeit not beneficial for adhesion of chondrocytes. A unique micro/nanopattern was employed to decouple cell spreading, cell shape, and cell-cell contact from RGD nanospacing. Under given spreading size and shape of single cells, the large RGD nanospacing was still in favor of preserving the normal phenotype of chondrocytes. Hence, the nanoscale spatial arrangement of cell-adhesive ligands affords a new independent regulator of cell dedifferentiation, which should be taken into consideration in biomaterial design for regenerative medicine.
细胞去分化在许多情况下都非常重要，例如软骨组织工程中软骨细胞在体外培养时的去分化这一经典问题。虽然细胞分化已经得到了广泛的研究，但细胞去分化的研究有限，细胞去分化的纳米线索报道甚少。在此，我们在非粘性聚乙二醇（PEG）水凝胶上制备了细胞黏附肽精氨酸-甘氨酸-天冬氨酸（RGD）的纳米图案和微/纳米图案，以研究 RGD 纳米间距对软骨细胞黏附和去分化的影响。相对较大的 RGD 纳米间距（大于 70nm）被发现可以增强二维培养中软骨细胞表型的维持，尽管不利于软骨细胞的黏附。采用独特的微/纳米图案将细胞铺展、细胞形状和细胞间接触与 RGD 纳米间距分离。在给定的单细胞铺展大小和形状下，较大的 RGD 纳米间距仍然有利于保持软骨细胞的正常表型。因此，细胞黏附配体的纳米级空间排列为细胞去分化提供了一个新的独立调控因子，这在再生医学中用于生物材料设计时应加以考虑。
