Scaffold Geometry-Imposed Anisotropic Mechanical Loading Guides the Evolution of the Mechanical State of Engineered Cardiovascular Tissues

Cardiovascular tissue engineering is a promising approach to develop grafts that, in contrast to current replacement grafts, have the capacity to grow and remodel like native tissues. This approach largely depends on cell-driven tissue growth and remodeling, which are highly complex processes that are difficult to control inside the scaffolds used for tissue engineering. For several tissue engineering approaches, adverse tissue growth and remodeling outcomes were reported, such as aneurysm formation in vascular grafts, and leaflet retraction in heart valve grafts. It is increasingly recognized that the outcome of tissue growth and remodeling, either physiological or pathological, depends at least partly on the establishment of a homeostatic mechanical state, where one or more mechanical quantities in a tissue are maintained in equilibrium. To design long-term functioning tissue engineering strategies, understanding how scaffold parameters such as geometry affect the mechanical state of a construct, and how this state guides tissue growth and remodeling, is therefore crucial. Here, we studied how anisotropic versus isotropic mechanical loading-as imposed by initial scaffold geometry-influences tissue growth, remodeling, and the evolution of the mechanical state and geometry of tissue-engineered cardiovascular constructs