Influence of cell and collagen concentration on the cell–matrix mechanical relationship in a corneal stroma wound healing model

The effect of different collagen and cell concentrations on the mechanical and remodeling behaviors of corneal stroma wound healing models consisting of collagen hydrogels seeded with human corneal fibroblasts during a 25 day culture period were examined. Human corneal fibroblasts were seeded at 1 × 105, 3 × 105 or 5 × 105 cells per hydrogel, and collagen concentrations of 2.5 mg/ml, 3.5 mg/ml or 4.5 mg/ml were examined. Two non-destructive techniques, spherical indentation and optical coherence tomography, were used to measure the elastic modulus and dimensional changes respectively at several time-points over the culture period. The elastic modulus of the hydrogels increased continuously over 25 days. Hydrogels with higher initial cell seeding densities and lower initial collagen concentrations were found to increase in elastic modulus faster and possessed a higher elastic modulus by the end of the culture period when compared to the other hydrogels. A mathematical equation was applied to accurately fit the change in elastic modulus over time. This study demonstrates a robust in vitro technique able to monitor the effect of different parameters on the cell–matrix mechanical relationship in a corneal stroma model during prolonged culture periods and enhances our understanding on corneal wound healing processes.

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► Non-destructively measuring the modulus of corneal fibroblasts in hydrogel for 25 days.
► Initial hydrogel and cell concentration affect the contraction and modulus increase.
► Hydrogels with high initial cell seeding densities increased in elastic modulus faster.
► Hydrogels with low initial collagen concentrations increased in elastic modulus faster.