Interdisciplinary Initiatives Program Round 4 – 2008

Peter Pinsky, Mechanical Engineering
Marc Levenston, Mechanical Engineering
Lane Smith, Orthopaedic Surgery
Christopher Ta, Opthalmology
Reinhold Dauskardt, Materials Science & Engineering

Connective tissues, which define bodily shape, must respond quickly, robustly and reversibly to deformations caused by internal and external stresses while performing a variety of mechanical functions in the body. For example, tendon transmits tension from a contracting muscle and articular cartilage forms a resilient coating on the ends of bones in synovial joints and resists forces generated by movement. Accurate computational models of connective tissue behavior are needed in order to predict the response of normal and pathological tissue in clinical applications and for providing principles for the rational design of functional tissue replacements.

Computer models of tissue mechanical behavior require that the stress-strain properties of the tissue be described in a mathematical model, known as the “constitutive equation.” The constitutive equation is usually based on standard engineering models such as elasticity and viscoelasticity and calibrated through experimental testing. The molecular and microscopic mechanisms that confer the unique properties of connective tissues have not been considered and the resulting models can demonstrably fail to describe some of the highly complex mechanical behavior found in living tissues. The need and challenge addressed in this project is to more closely relate engineering modeling concepts to the unique molecular-level mechanisms in the tissue extracellular matrix that are fundamentally responsible for the mechanical behavior of connective tissues.

This project focused on a particular and interesting connective tissue – the human cornea. Like all connective tissues, the cornea is a system of insoluble fibrils (collagen) and soluble proteoglycan polymers which assemble and interact to carry the tissue stresses. Because the transparency of the cornea requires that the collagen fibrils and attached proteoglycans assume a highly regular arrangement that can be imaged and measured, it is an ideal tissue for our initial investigations. We have created a theoretical model of the cornea that predicts the mechanical behavior of the tissue based on the intrinsic properties of its molecular constituents propagated through the tissue’s hierarchical structures. For example, we have predicted the shear and swelling properties of the tissue in terms of the electrolytic features of the tissue and validated these predictions by direct experimental measurements. We have shown that the electrical properties of the tissue are crucial players in the way in which the tissue works and this understanding is vital for accurate modeling. There is currently tremendous innovation in ophthalmology where clinicians seek to improve vision by modification of the cornea by various means – and all in need of accurate modeling for understanding and predictive assessment. Likewise, the goal of constructing an artificial cornea can be achieved only when a full understanding of the mechanics of the native tissue is in hand.