Mechanical Strain-Stimulated Remodeling of Tissue-Engineered Blood Vessel Constructs

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Abstract
Progress in tissue-engineering research has renewed optimism about the possibility of constructing a physiologically functional blood vessel substitute in the laboratory. To this end, we have explored the use of defined mechanical stimulation to further the development of vascular tissue analogs. We now report our findings on smooth muscle cell and fibroblast-seeded collagen constructs exposed to 10% cyclic strain for 4 or 8 days. Our results demonstrate that 4-day strained constructs exhibit an enhancement of mechanical properties, likely through the remodeling actions of matrix metalloproteinase 2 (MMP-2). Strain-stimulated expression of MMP-2 is accompanied by alterations in elastin and collagen gene expression. In the context of tissue engineering a blood vessel construct, we report that strain-stimulated regulation of MMP-2 activity could have a favorable impact on the structural development of the constructs whereas overexpression of MMP-2 during prolonged exposure to strain (8 days) could have adverse consequences on the structural integrity of the tissue analogs. Taken together, these results illustrate the importance of mechanical stimulus as a major regulatory component of tissue-engineered blood vessel remodeling.