Sun M G, Luo Y, Teng T, Guaiquil V, Zhou Q, McGinn L, Nazzal O, Walsh M, Lee J, Rosenblatt M I
Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, 1855 W. Taylor St., Chicago, IL 60612.
Department of Bioengineering, University of Illinois at Chicago, 851 S. Morgan St., Chicago, IL 60607.
Macromol Chem Phys. 2021 Apr;222(7). doi: 10.1002/macp.202170013. Epub 2021 Apr 5.
Silk fibroin films are excellent candidate biomaterials for corneal tissue engineering due to their optical transparency, biocompatibility, and mechanical strength. Their tunable chemical and mechanical properties open the possibility of engineering cellular microenvironments that can both mimic native corneal tissue and provide stimuli to actively promote wound regeneration. While silk film mechanical properties, such as surface topography, have demonstrated the ability to control corneal epithelial cell wound regenerating behavior, few studies have explored the stiffness tunability of these films and its cellular effects. Cells are known actively sense the stiffness of their surroundings and processes such as cell adhesion, migration, proliferation, and expression of stem markers can be strongly influenced by matrix stiffness. This study develops technical solutions that allow for both the fabrication of films with stiffnesses similar to corneal tissue and also for their characterization in an aqueous, native-like environment at a scale relevant to cellular forces. Physiological evidence demonstrates that corneal epithelial cells are mechanosensitive to films of different stiffnesses and show that cell spreading, cytoskeletal tension, and molecular mechanotransducer localization are associated with film stiffness. These results indicate that silk film stiffness can be used to regulate cell behavior for the purposes of ocular surface repair.
丝素蛋白膜因其光学透明性、生物相容性和机械强度，是角膜组织工程的优秀候选生物材料。其可调节的化学和机械性能为构建细胞微环境提供了可能性，这种微环境既能模拟天然角膜组织，又能提供刺激以积极促进伤口再生。虽然丝素蛋白膜的机械性能，如表面形貌，已证明能够控制角膜上皮细胞伤口再生行为，但很少有研究探讨这些膜的硬度可调性及其细胞效应。已知细胞能主动感知周围环境的硬度，细胞黏附、迁移、增殖和干细胞标志物表达等过程会受到基质硬度的强烈影响。本研究开发了技术方案，既能制造出硬度与角膜组织相似的薄膜，又能在与细胞力相关的尺度上，在类似天然的水性环境中对其进行表征。生理学证据表明，角膜上皮细胞对不同硬度的薄膜具有机械敏感性，并表明细胞铺展、细胞骨架张力和分子机械转导器定位与薄膜硬度有关。这些结果表明，丝素蛋白膜的硬度可用于调节细胞行为，以实现眼表修复的目的。
