Quality Thresholds for Angiogenesis Under Acoustic Manipulation in Engineered Vascular Tissues

Tissue engineering can be accomplished in a plethora of ways, ranging from direct deposition of cells onto scaffolds and chips to contactless volumetric printing of 3D structures. Recent studies have examined the feasibility of using acoustic manipulation of cells in vitro and in situ, although these studies have not yet identified the critical quality requirements to create complex tissues. To this end, we present a methodology for generating and evaluating acoustically patterned 3D vascular tissue for biomedical studies. Over a period of 7 days, tissues were able to generate self-assembling vasculature, deposit a self-secreted extracellular matrix network, and demonstrate changes in angiogenic gene expression in response to acoustic patterning. These behaviors demonstrated a positive correlation between the quality of alignment and associated vascular structure following acoustic manipulation, suggesting a relationship between patterning and tissue development. These findings identify necessary requirements for creating self-assembling vasculature in vitro, accounting for biological and physical parameters.