Soft skeletal connective tissues perform important mechanical functions. To function effectively, these tissues must develop and maintain material properties that allow them to withstand the mechanical loading imposed on them. The material properties are determined by the tissue composition and microstructure. Currently, we have only a limited understanding of how these tissues alter their composition and microstructure. and consequently their material properties, in response to mechanical loading.

Previous studies have suggested that tensile strains stimulate the production of collagen fibers, while compressive stresses stimulate proteoglycan synthesis. Collagen fibers give the tissues their tensile properties, while proteoglycans affect compressive behavior. To improve our understanding of these relationships between microstructure. material properties, and mechanical loading, this thesis presents four studies that investigate the effects of microstructure and mechanical loading on the material properties of soft skeletal connective tissues.

The first study relates tensile behavior to composition and microstructure. It presents a mathematical model that describes uniaxial tensile constitutive and failure behavior based on microstructural parameters including fiber volume fraction, fiber orientations, fiber crimping and failure strain, collagen type, cross-link density, and ground substance resistance to fiber reorientation. The model can reproduce the tensile behavior of tendon, meniscus, and articular cartilage. It provides a consistent microstructural approach for describing the tensile behavior of a wide range of soft skeletal connective tissues.

The second study examines the effects of tensile loading on the geometric and material properties of tendons and ligaments. It presents a computational model that relates changes in tendon and ligament cross-sectional area, modulus, and strength to time-dependent biological influences and to cyclic tensile strains. The model can describe both normal development and adaptation to exercise, immobilization, and remobilization. It represents an important first step in elucidating the basic principles that govern the adaptation of soft skeletal connective tissues to tensile loading.

The third study relates compressive behavior to composition and microstructure. It proposes quantitative relationships that estimate tissue permeability from water content, glycosaminoglycan content, and collagen fiber diameter. It also presents theoretical analyses examining the effects of permeability and load rate on the compressive behavior of tissue specimens loaded in uniaxial confined compression. The analyses suggest that while tendon, meniscus, and articular cartilage all exhibit a linear constitutive behavior, tendon deforms much more than the other tissues because of its low glycosaminoglycan content and high permeability. This study establishes relationships that quantify the effects of composition and microstructure on the compressive behavior of soft skeletal connective tissues.

The fourth study considers the effects of compressive loading on the material properties of tendons that wrap around bones. It proposes a quantitative remodeling rule that predicts the development of a low permeability region in the tendon in response to high cyclic hydrostatic pressures. Finite element analyses of the rabbit flexor digitorum profundus tendon suggest that the low permeability protects the solid constituents of the extracelluar matrix from deformations that might damage the matrix organization. This study provides insight into both the mechanical stimuli and the mechanical consequences of the tissue adaptation to compressive loading.

The relationships examined in this thesis are fundamental to understanding the normal development and function of soft skeletal connective tissues. They are also essential to understanding the processes by which these tissues adapt to their biomechanical environments. An understanding of these inherent adaptive capabilities may allow the development of innovative treatments for rehabilitating, repairing, and regenerating damaged soft skeletlal connective tissues. This thesis lays the groundwork for building the necessary understanding of the interplay between composition and microstructure, material properties, and mechanical loading.