Cyclic mechanical strain stimulates in vitro remodeling of tissue engineered vascular grafts

It is a well-known fact that living tissue has remodeling capabilities within the human body. However, whether such remodeling can be reproduced in vitro has yet to be determined. The authors examine this conundrum by using the novel approach of stimulating vascular cells embedded in a viscoelastic collagen gel under cyclic mechanical strain. Cellular response to stimulation is determined by assessing matrix production within the constructs. The authors´ findings suggest that cells subjected to cyclic mechanical strain respond by remodeling their extracellular environment through both production of new ECM and ECM degradation. In addition, cells exercise control of production and activation of matrix degrading enzymes, also known as matrix metalloproteinases (MMPs) based on mechanical stimuli. Preliminary data suggest that subjecting constructs to 4 and 8 days of mechanical strain increases the levels of at least one enzyme involved in collagen metabolism, MMP-2. A similar effect was noted upon collagen mRNA. These findings indicate a complex remodeling of the matrix, activated specifically through exposure to mechanical stimulus. Thus, in vitro remodeling may be used as a powerful tool in the development of a three-dimensional construct with appropriate mechanical and biochemical composition. The use of cyclic mechanical strain to activate such remodeling has been demonstrated here with vascular constructs