Tissue Engineering of 3D Organotypic Microtissues by Acoustic Assembly

Abstract

There is a rapidly growing interest in generation of 3D organotypic microtissues with human physiologically relevant structure, function, and cell population in a wide range of applications including drug screening, in vitro physiological/pathological models, and regenerative medicine. Here, we provide a detailed procedure to generate structurally defined 3D organotypic microtissues from cells or cell spheroids using acoustic waves as a biocompatible and scaffold-free tissue engineering tool.

Keywords: 3D organotypic microtissues; Acoustic assembly; Acoustic waves; Cardiac scaffold; Cardiomyocyte; Cell assembly; Cell spheroids; In vitro tissue model; Regenerative medicine; Spheroid assembly; Tissue engineering.

Fig. 1

Illustration of acoustic node assembly of organotypic microtissues. Cells/spheroids are first loaded in the assembly chamber. Then standing waves are applied to assemble cells/spheroids into pre-defined patterns based on node and antinode zones on standing waves in a fluidic environment. Further assembled cells/spheroids are immobilized in fibrin hydrogel and maturated in culture media

Fig. 2

Schematic of experimental setup for acoustic assembly

Fig. 3

Schematic of optimized chemically defined cardiac differentiation protocol [10]