Silk Film Stiffness Modulates Corneal Epithelial Cell Mechanosignaling

Abstract

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 to 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.

Recent Advances in Natural Materials for Corneal Tissue Engineering

“…Silk fibroin, a natural protein extracted from Bombyx mori cocoons, can be formed into films and scaffolds with tunable degradation and mechanical strength with non-immunogenic responses in vivo [ 38 , 80 , 81 ]. Use of silk fibroin as a film or scaffolds for corneal tissue replacement [ 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 ] remains an active area of research, as outlined in Table 3 . Silk films and membranes can be fabricated through simple evaporation or electrospinning.…”

“…Silk films and membranes can be fabricated through simple evaporation or electrospinning. Silk films prepared with differing methanol concentrations, a technique to induce β-sheet crystallinity within the secondary structure of the silk polymer, resulted in elastic modulus values ranging from 13–445 kPa [ 82 ]. Furthermore, a centrifugal casting technique has been developed to improve the mechanical properties of silk films [ 83 ].…”

Recent Research Progress of Ionic Liquid Dissolving Silks for Biomedicine and Tissue Engineering Applications

“…Hence, SF can provide broad application prospects for the design of new biomaterials due to its biocompatibility, excellent mechanical properties, air and moisture permeability and good processability [ 11 ]. After degumming, SF can be prepared into different forms of materials, such as film [ 19 ], gel [ 20 ], microcapsule [ 21 ], 3D printed scaffold [ 22 ], fiber [ 23 , 24 ] and micro/nano particle [ 25 ] among others. These materials can be applied for drug delivery [ 21 , 26 ], wound healing [ 20 , 27 ], tissue engineering [ 28 , 29 ] and environment-related applications as well as in the energy sector [ 30 ].…”