Multiscale mechanics and experimental investigation of the human cornea [electronic resource]

The unique hierarchical structure of the human cornea results in a tissue which is remarkably transparent but mechanically resilient enough to protect the contents of the eye and maintain its shape for appropriate refraction of light onto the retina. Since the eye generates an intraocular pressure, the cornea can be thought of as part of a pressure vessel under constant mechanical stress. This work aims to use the latest knowledge and imaging at multiple length scales to produce a comprehensive biomechanical model of the cornea. Examining a cross-section of the human cornea with second harmonic-generated (SHG) imaging reveals that many lamellae (collagen-filled, tape-like fibers that make up the main stroma layer) have inclined trajectories that take them through the corneal thickness with a depth-dependent distribution. Transverse shear moduli from 1% shear strain oscillatory tests were found to be two to three orders of magnitude lower than tensile moduli reported in the literature and six times higher in the anterior third than the posterior third, confirming the hypothesis. In order to create a theoretical model that accounts for the 3-D collagen architecture, a multiscale model of stromal elasticity is developed. At the nanoscale, a collagen fibril is built by assembling tropocollagen molecules with enzymatic and non-enzymatic covalent crosslinks. Crosslink density, which is a function of age, disease, and therapeutic treatment, strongly influences fibril stiffness and is a key feature of the present model. At the microscale, aligned collagen fibrils are combined with other components to form a single lamella (fiber). For a continuum mechanics-based model of the lamella, a hyperelastic strain energy density is defined that is decomposed into three parts. At the macroscale, these directional lamellae organize to construct the stroma with a spatially-varying distribution of orientation. Stromal elasticity is calculated by a weighted average of individual lamella properties based on the spatially-varying orientation distribution. A fully 3-D representation of lamella orientation is synthesized by combining data from SHG imaging and X-ray diffraction. Inclined lamella orientation is extracted from SHG images and characterizes how the range and distribution of lamellae at inclined angles varies with depth through the stroma. Direct measurements from X-ray diffraction experiments give the depth-dependent orientation of lamellae in the tangent plane that follows the corneal surface. The model is calibrated with reference to macroscale in vitro inflation and torsional shear experiments. Nanoscale tropocollagen parameters and resulting fibril properties match well with molecular simulations and nanoscale experiments in the literature. Simulated experiments for model validation include in vivo indentation, in vitro strip extensiometry, and in vitro free swelling studies. Important features of the model are showcased by varying lamellar orientation distributions and non-enzymatic crosslink density.

Keywords: Mechanical Engineering.
Advisor: Pinsky Peter M. (Peter Michael)
Kuhl Ellen
Levenston Marc Elliot advisor. Thesis advisor