Mechanical Properties of Bioengineered Corneal Stroma

Abstract

For the majority of patients with severe corneal injury or disease, corneal transplantation is the only suitable treatment option. Unfortunately, the demand for donor corneas greatly exceeds the availability. To overcome shortage issues, a myriad of bioengineered constructs have been developed as mimetics of the corneal stroma over the last few decades. Despite the sheer number of bioengineered stromas developed , these implants fail clinical trials exhibiting poor tissue integration and adverse effects in vivo. Such shortcomings can partially be ascribed to poor biomechanical performance. In this review, existing approaches for bioengineering corneal stromal constructs and their mechanical properties are described. The information collected in this review can be used to critically analyze the biomechanical properties of future stromal constructs, which are often overlooked, but can determine the failure or success of corresponding implants.

Keywords: bioengineering; corneas; mechanical properties; stromal layers.

Figure 1

Schematic illustration of an injured human cornea undergoing either uncontrolled or controlled regeneration of the stroma. An uncontrolled regeneration process (top half of the illustration) can be caused, for instance, by an untreated severe injury of the stroma or following implantation of an unsuitable stromal construct, which causes an irreversible keratocyte‐to‐(myo)fibroblast transition as well as disorganized extracellular matrix (ECM) production. A controlled regeneration process (bottom half of the illustration) can be aided by a suitable bioengineered stromal implant that integrates well into the hosting tissue and therefore fosters native keratocyte infiltration, reversible keratocyte‐to‐fibroblast transition as well as a slow and organized ECM deposition and replacement.

Figure 2

On the left, a schematic cross‐sectional representation of the corneal anatomy illustrates the five main layers of the cornea: starting from the top: the epithelium (green), the Bowman’s layer, the stroma (gray), the Descemet’s membrane and the endothelium (red). On the right, a scanning electron microscopy (SEM) image of a cross section of the corneal stroma shows the organization of the collagen lamellae within the stroma (original work by the authors). Briefly, the tissue was decellularized in 10% sodium hydroxide solution (Merck) at room temperature for 6 days before it was fixed with 1% osmium tetroxide (Electron Microscopy Sciences), dehydrated in a graded series of ethanol (70%–90%–100%, Merck) and cut with a razor blade. After coating with 10 nm gold in a sputter coater (Cressington 108auto), it was transferred to a Scios DualBeam SEM (magnification 2500, 5 kV, ThermoFisher Scientific) for imaging.

Figure 3

a) Ashby plot of the Young's modulus and ultimate tensile strength showing mechanical characteristics of human tissues including the cornea in comparison to some polymers used in ophthalmic applications and other commonly known materials. b) Ashby plot showing the mechanical properties of the human cornea compared to corneal constructs. The dashed‐line circle includes a wider range of values reported in literature for the Young's modulus of the cornea, while the continuous‐line circle illustrates a more consistently reported range of values, which is in agreement with most of the studies that present bioengineered stromal implants in this review.

Figure 4

Examples of common materials, material modifications, and fabrication techniques that are used for the engineering of stromal constructs. Together, these should contribute to a stromal construct with sufficient mechanical properties, optical properties and biocompatibility.