Geometric and Mechanical Patterning of Hierarchical Vascular Network

Blood supply is a fundamental need for tissue viability. Without a stable hierarchical vessel network to provide oxygen and nutrients, cells cannot survive once the tissue dimensions grow beyond several hundred microns due to diffusive limitations. The process of vasculogenesis followed by angiogenesis during development has been described extensively in the literature. However, the role of physical signals including internal and external mechanical forces on the spatial organization of complex hierarchical vasculature is not fully clear. In this research we propose that mechanical loading can direct sprouts orientation from macro-vessels, as well as orientation of micro-vessel network, and could enhance the connectivity between macro and micro vessel networks. Using CAD software, a stretchable device is designed and fabricated. The new experimental assay enables the application of external mechanical force on macro-vessel model. The preliminary results show a guidance effect of sprouting growth with correlation to static stretch orientation. Furthermore, lateral stretch leads to increased sprouting events and results in higher sprout length. In contrary, longitudinal stretch decreases sprouting development as reflected in lower sprouts number and length. These results demonstrate the role of mechanical loading on sprouting stimulation and guidance, and may lead to new strategies for controlling hierarchical vasculature architecture within engineered tissues.