Acoustofluidic Engineering of Functional Vessel-on-a-Chip

Abstract

Construction of in vitro vascular models is of great significance to various biomedical research, such as pharmacokinetics and hemodynamics, and thus is an important direction in the tissue engineering field. In this work, a standing surface acoustic wave field was constructed to spatially arrange suspended endothelial cells into a designated acoustofluidic pattern. The cell patterning was maintained after the acoustic field was withdrawn within the solidified hydrogel. Then, interstitial flow was provided to activate vessel tube formation. In this way, a functional vessel network with specific vessel geometry was engineered on-chip. Vascular function, including perfusability and vascular barrier function, was characterized by microbead loading and dextran diffusion, respectively. A computational atomistic simulation model was proposed to illustrate how solutes cross the vascular membrane lipid bilayer. The reported acoustofluidic methodology is capable of facile and reproducible fabrication of the functional vessel network with specific geometry and high resolution. It is promising to facilitate the development of both fundamental research and regenerative therapy.

Recent progress on acoustofluidic manipulation of cells and particles

“…Currently, the focus in the development of acoustic radiation for micrometer-sized particle manipulation is on deriving complex structures and achieving flexible manipulation. On the structure construction aspect, recent progress for using acoustic radiation force for deriving heterotypic cell spheroids [86], vessels [87], and organoids [88][89][90], indicate the capability of acoustic radiation force for noncontact manipulation. Achieving the forming of more complicated structures with higher heterogeneity, which indicate a targeted manipulation of specific population of particles or cells, would be a research direction for meeting application side requirements.…”

Acoustofluidic Actuation of Living Cells

“…In applications where parallel line arrays are desired, such as in the engineering of strip-structured tissues like blood vessels, acoustofluidic patterning has demonstrated significant potential [107][108][109]. Kang et al aligned endothelial cells into parallel arrays using acoustofluidics, which improved endothelial cell-cell interactions and gene expression, thus enhancing vascular tissue regeneration [110].…”

Microphysiologically Engineered Vessel-Tumor Model to Investigate Vascular Transport Dynamics of Immune Cells

“…The microfluidic technique offers a flexible approach to engineer tumor-on-chip platforms and recreates vascular transport in vitro. − Several studies focus on the early stage of vascularization and manipulate different strategies to promote the growth of endothelial cells around the tumor by altering the microphysiological environment. − Dey et al explored the cytotoxicity induced by CAR-T in the breast tumor microenvironment based on blood vessels and dynamic flow . Similarly, Ayuso et al used a microfluidic model to simulate and study NK cell migration, cytotoxicity, and antibody-dependent cytotoxicity in complex 3D structures .…”