The fibrocartilaginous meniscus plays a crucial role in knee joint function by providing load support, distribution and stability. Cells of the meniscus respond to mechanical loading both in vivo and in vitro in order to maintain extracellular matrix organization. Importantly, meniscus cells exhibit dramatic differences in morphology and gene expression depending on their spatial location that are associated with variations in tissue mechanics. These anatomical differences are expected to regulate spatial variations of mechanics in the immediate vicinity or micromechanical environment of meniscus cells and therefore may regulate their phenotype.
The objective of this dissertation was to describe the micromechanical environment of meniscus cells localized to different regions of the tissue using computational models and experimental measurements of strain. The computational models accounted for important anatomical features of meniscus cells and the extracellular matrix including time-dependent mechanics, matrix anisotropy, a mechanically distinct pericellular matrix, and region-specific cell geometries as measured here using confocal microscopy and three-dimensional reconstruction. Multiscale, biphasic finite element models incorporating these physical and morphological features predicted that rounded inner meniscus cells (maximum aspect ratio: 1.2-2.4) may experience stable volumes and higher strain amplifications yet lower strain magnitudes as compared to elongated cells of the outer meniscus (maximum aspect ratio: 1.6-5.1).
In addition, a custom deformation device was designed, validated, and combined with confocal microscopy and texture correlation to measure strain at length scales representative of meniscus tissue and cells. Results from these studies provide the first experimental measurements of strain surrounding meniscus cells. Furthermore, these results demonstrate that strains in the microenvironment of meniscus cells may be amplified from (greater than 1.2 fold), similar to, or attenuated from (less than 0.6 fold) strains in the tissue. Importantly, the results also suggest that strain transfer may be dependent on the microscale matrix architecture; for example, cells within aligned collagen fibers may experience attenuated strains along the direction of applied deformation while cells within homogeneous matrix regions or those representative of a fiber junction experienced amplified strains. This study supports the need for computational models that account for a heterogeneous cell and matrix structure.
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