The influence of substrate topography on the migration of corneal epithelial wound borders

Abstract

Currently available artificial corneas can develop post-implant complications including epithelial downgrowth, infection, and stromal melting. The likelihood of developing these disastrous complications could be minimized through improved formation and maintenance of a healthy epithelium covering the implant. We hypothesize that this epithelial formation may be enhanced through the incorporation of native corneal basement membrane biomimetic chemical and physical cues onto the surface of the keratoprosthesis. We fabricated hydrogel substrates molded with topographic features containing specific bio-ligands and developed an in vitro wound healing assay. In our experiments, the rate of corneal epithelial wound healing was significantly increased by 50% in hydrogel surfaces containing topographic features, compared to flat surfaces with the same chemical attributes. We determined that this increased healing is not due to enhanced proliferation or increased spreading of the epithelial cells, but to an increased active migration of the epithelial cells. These results show the potential benefit of restructuring and improving the surface of artificial corneas to enhance epithelial coverage and more rapidly restore the formation of a functional epithelium.

Real-Time Monitoring of Wound Healing on Nano-Patterned Substrates: Non-Invasive Impedance Spectroscopy Technique

“…A similar finding has been obtained where gratings oriented surface, perpendicular to the wound, induces a significant enhancement of cell polarization, migration speed and directionality, resulting in faster wound coverage [16]. The rate of wound healing of corneal epithelium has increased significantly with topographically featured substrates made of poly(ethylene glycol) diacrylate (PEGDA) hydrogel compared to flat substrates [17].But, all of these reports perform time lapse imaging followed by its processing to assess the cellular behavior like rate of wound healing on topographical substrates, directionality of cellular migration, nature of focal adhesion and others. There are no reports of non-invasive electrical monitoring of wound healing phenomena on nano/micro structured surfaces.…”

Materials as stem cell regulators

“…Parallel microgrooves (10 μM groove width) on the surface of cell-adhesive substrates were recently used to replace the effects of small-molecule epigenetic modifiers and significantly improve the efficiency of cellular reprogramming 118 . Other noteworthy strategies have attempted to control the nanometre-scale organization of cell-adhesive areas by patterning cell-adhesive gold nanodots 119 , or using nanopatterned block copolymer stencils to form synthetic hydrogels 120 . An interesting future direction could involve dynamically varying the nanometre-scale topography or cell-adhesive regions on a substrate, and then observing responsive changes in stem cell phenotype 31 .…”

Microgrooved collagen-based corneal scaffold for promoting collective cell migration and antifibrosis

“…32,33 In addition, some studies have broached that patterned surfaces can promote the migration of corneal epithelial cells. 34,35 Therefore, the topography-cell interaction could be combined with corneal tissue engineering to develop a micropatterned scaffold that is able to regulate cells. Such strategy may reduce keratocyte differentiation and accelerate corneal epithelial cell migration, which not only helps regulate corneal cell behavior but also mimic the in vivo microenvironment of the native cornea.…”