Multiscale structure-function relationships in the mechanical behavior of tendon and ligament

Abstract

Ligaments and tendons are dense, fibrous connective tissue that transmit and bear loads within the musculoskeletal system. They are elastic and viscous, and thus are capable of storing and dissipating energy. Although soft and flexible, they can interface with materials that are orders of magnitude stiffer (e.g., bone) and orders of magnitude more compliant (e.g., muscle). These functions are mediated by a complex network of hierarchically organized fibrillar collagen and accessory proteins and molecules. Tissue constituents form unique structural motifs that span the nanoscale, microscale, mesoscale and macroscale. This multiscale organization enables both a robust mechanical response at the macroscopic joint level and simultaneously provides a microscale environment conducive to cellular proliferation and nutrient transport.

The aim of this dissertation was to gain a deeper understanding of how the organization of tissue constituents contribute to mechanical function of tendon and ligament across scale levels. At the nanoscale, the question regarding the role of the proteoglycan decorin was addressed. A novel combination of an in vitro assay, imaging techniques and mechanical testing was used to explore how decorin acts to modify the strength of collagen fibril networks. At the microscale, computational modeling was used to examine how different fibril organizations contribute to the macroscopic volumetric response of tendon and ligament during tensile loading. The volumetric response is believed to drive fluid flux within the tissue, which may play a role in nutrient transport and the apparent viscoelastic response. This flow dependent mechanism was addressed in a study that experimentally measured the volumetric changes in mesocale fascicles during viscoelastic testing. One of the challenges in discerning structure-function relationships in tendon and ligament is the large number of uncontrolled variables, which can be difficult to account for in an experimental setting. To address this challenge, a collagen based tendon surrogate was developed for use as a physical model. The physical model was coupled to a validated micromechanical computational model. This facilitated the testing of hypotheses that would have been difficult to address experimentally. The four studies contained within this dissertation, along with a number of preliminary studies, represent a novel contribution to the field of tendon and ligament mechanics.