The role of the stress environment on fibrocartilage development

Cells are highly sensitive to their mechanical environment. Understanding the role of the stress environment (e.g., compressive vs. tensile) on tissue development will allow us to engineer replacements for tendons and their fibrocartilaginous bony insertions. We formulated exact linear elasticity and a finite element solution that offered insight into the nature of the compressive environment needed for fibrocartilage formation. The solutions led us to hypothesize that only a single compressive principal stress component is needed to induce cells to synthesize fibrocartilage. These solutions were then validated in an in vitro model. Collagen matrices were seeded with mesenchymal stromal cells and loaded cyclically for 7 days. Immuno-fluorescence was used to determine cell shape, cell orientation, collagen II production, and aggrecan production. We hypothesized that compressive stresses promote the production of fibrocartilage while tensile stresses promote the production of aligned collagenous tissue. This hypothesis was supported by our results: cells in the compressive region were "rounder" than cells in the tensile region, cells in the tensile region aligned with the direction of tension, while the cells in the compressive region had a random orientation, and cells embedded in the collagen matrices produced both aggrecan and type II collagen (components of fibrocartilage).