The intervertebral disc is a highly heterogeneous tissue that plays a central role in load support and flexibility of the spine. The disc integrity is maintained by disc cells which have been demonstrated to exhibit dramatic differences in morphology and biologic responses to mechanical stimuli in the nucleus pulposus, inner and outer anulus fibrosus regions. Disc cells are surrounded by a pericellular matrix that may significantly influence micromechanics of the contained cells. And the micromechanical stimuli that cells experience are potentially key regulators of biologic responses occurred in disc degeneration and regeneration.

The objective of this dissertation was to describe the micromechanics, such as stress and strain, fluid pressure and flow, of disc cells localized to different regions using three-dimensional computational models based on in situ morphology. The morphology of the pericellular matrix and cells were obtained in situ using fluorescence confocal microscopy and three-dimensional reconstruction, showing significant variations across regions with distinct pericellular matrix aspect ratios (largest/smallest diameter) in the nucleus pulposus (average of 1.9), and in the inner (2.4) and outer anulus fibrosus (2.8). Pericellular matrix regions containing 1 or 2 cells were the dominant subgroup in the disc while multicellular pericellular regions were present more often in the younger nucleus pulposus and outer anulus fibrosus.

Three-dimensional finite element models of cell-matrix interaction were constructed using region-specific geometry registered from in situ morphology, region-specific material properties and boundary conditions, with incorporation of biphasic behaviors, linear elasticity and anisotropy of the extracellular matrix. Disc cells were predicted to experience higher strain (strain amplification ratio from the extracellular matrix:​ 1.8-3.8) and lower stress at equilibrium, compared to the pericellular matrix (1.6-2.1), with magnitudes dependent on the cell size, shape, relative position and number of cells within one pericellular matrix as well as the region of cell origin. The predicted fluid pressurization rate and pattern of disc cells appeared to depend also on the local in situ geometry of the pericellular matrix in addition to cellular characteristics mentioned above. These studies provide quantitative information on micromechanical stimuli that cells may experience in the cell-matrix interaction in the intervertebral disc.