White Corina, DiStefano Tyler, Olabisi Ronke
Biomedical Engineering, The State University of New Jersey, Rutgers University, Piscataway, New Jersey.
Neurobiology, Neurodegeneration, and Repair, National Eye Institute, Bethesda, Maryland.
J Biomed Mater Res A. 2017 May;105(5):1260-1266. doi: 10.1002/jbm.a.35992. Epub 2017 Feb 13.
Although transplantation of retinal pigment epithelial (RPE) cells has shown promise for the treatment of retinal degenerative diseases, this therapeutic approach is not without challenges. Two major challenges are RPE cell dedifferentiation and inflammatory response following transplantation. The aim of this work is to understand how the rigidity of a scaffold, a relatively unexplored design aspect in retinal tissue engineering, affects RPE cells, particularly the pathways associated with the aforementioned challenges. Poly(ethylene glycol) diacrylate (PEGDA) of varying molecular weights from 3.4 to 20 kDa were photopolymerized to fabricate scaffolds. The Young's modulus of the scaffolds varied from 60 to 1200 kPa. A cell study was then conducted to test the effects of scaffold rigidity on RPE cells. A cell adhesion peptide motif of arginine-glycine-aspartic acid-serine (RGDS) was conjugated to 60 and 1200 kPa scaffolds and ARPE-19 cells, a human RPE cell line, were seeded onto these hydrogels. Cells grown on scaffolds demonstrated qualitatively different adhesion properties, metabolic activity, and gene expression at an mRNA level. IL-6 and MCP-1, two inflammation markers known to recruit microglial into the retina, had the same expression pattern with cells having the highest expression on the high modulus scaffold and lowest expression on the control substrate. This study demonstrates that scaffold rigidity, an important design parameter in other areas of tissue engineering, affects cell adhesion, activity, and expression of RPE cells. Though more exploration is needed, this begins to lay a foundation for optimizing scaffold rigidity to promote long-term success of RPE scaffolds. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1260-1266, 2017.
尽管视网膜色素上皮（RPE）细胞移植已显示出治疗视网膜退行性疾病的潜力，但这种治疗方法并非没有挑战。两个主要挑战是RPE细胞去分化和移植后的炎症反应。这项工作的目的是了解支架的刚度（视网膜组织工程中一个相对未被探索的设计方面）如何影响RPE细胞，特别是与上述挑战相关的途径。将分子量从3.4 kDa到20 kDa不等的聚（乙二醇）二丙烯酸酯（PEGDA）进行光聚合以制造支架。支架的杨氏模量从60 kPa到1200 kPa不等。然后进行细胞研究以测试支架刚度对RPE细胞的影响。将精氨酸 - 甘氨酸 - 天冬氨酸 - 丝氨酸（RGDS）的细胞粘附肽基序与60 kPa和1200 kPa的支架偶联，并将人RPE细胞系ARPE - 19细胞接种到这些水凝胶上。在支架上生长的细胞在mRNA水平上表现出定性不同的粘附特性、代谢活性和基因表达。白细胞介素 - 6（IL - 6）和单核细胞趋化蛋白 - 1（MCP - 1）是已知可将小胶质细胞募集到视网膜中的两种炎症标志物，它们具有相同的表达模式，即在高模量支架上细胞表达最高，在对照底物上表达最低。这项研究表明，支架刚度作为组织工程其他领域的一个重要设计参数，会影响RPE细胞的粘附、活性和表达。尽管还需要更多的探索，但这开始为优化支架刚度以促进RPE支架的长期成功奠定基础。©2017威利期刊公司。《生物医学材料研究杂志》A部分：105A：1260 - 1266，2017年。
