The Effect of Mechanical Loading on Sprouting Angiogenesis from Engineered Macro-vessel Model

The influence of mechanical signals on sprouting angiogenesis has been of interest in the field of tissue engineering and biomechanics. Here, a unique experimental methodology is developed to apply mechanical loading on an engineered macro-vessel model to study the influence on angiogenic sprouting. The polydimethylsiloxane (PDMS) stretchable device contains an engineered macro-vessel embedded within a collagen matrix. The model is loaded either parallel or perpendicular to the macro-vessel (longitudinal or lateral, respectively). A finite element analysis is performed to characterize the strain maps of the PDMS-collagen setup. The results indicate high uniform strain around the macro-vessel perimeter under longitudinal loading, while lateral loading results in low strain in the horizontal direction and high strain along the vertical direction. Experimental results for lateral loading show increased sprouting events and capillary orientation in the stretch direction following the organization of matrix fibers, while longitudinal loading results in sprouting inhibition. These findings allow prediction of angiogenic sprouting under specified mechanical loading profiles and may serve as a tool to rationally design and control vascular network architecture by physical means. Finally, the presented approach can serve as a platform for studying cell behavior under mechanical loading for any physiological tubular duct or vessel model.