Page 269 - IJB-9-4

International Journal of Bioprinting

RESEARCH ARTICLE
High-throughput fabrication of cell spheroids

with 3D acoustic assembly devices

Tingkuan Miao , Keke Chen 1,2† *, Xiaoyun Wei , Beisi Huang , Yuecheng Qian ,
1,2
1
1
1†
Ling Wang *, Mingen Xu *
1,2
1,2
1 School of Automation, Hangzhou Dianzi University, Hangzhou 310018, China
2 Key Laboratory of Medical Information and 3D Bioprinting of Zhejiang Province, Hangzhou Dianzi
University, Hangzhou 310018, China
Abstract

Acoustic cell assembly devices are applied in cell spheroid fabrication attributed to
their rapid, label-free and low-cell damage production of size-uniform spheroids.
However, the spheroids yield and production efficiency are still insufficient to meet
the requirements of several biomedical applications, especially those that require
large quantities of cell spheroids, such as high-throughput screening, macro-scale
tissue fabrication, and tissue repair. Here, we developed a novel 3D acoustic cell
assembly device combined with a gelatin methacrylamide (GelMA) hydrogels for
the high-throughput fabrication of cell spheroids. The acoustic device employs three
† These authors contributed equally
to this work. orthogonal piezoelectric transducers that can generate three orthogonal standing
bulk acoustic waves to create a 3D dot-array (25 × 25 × 22) of levitated acoustic
*Corresponding authors:
Keke Chen nodes, enabling large-scale fabrication of cell aggregates (>13,000 per operation).
(kkchen@hdu.edu.cn) The GelMA hydrogel serves as a supporting scaffold to preserve the structure of cell
Ling Wang aggregates after the withdrawal of acoustic fields. As a result, mostly cell aggregates
(lingw@hdu.edu.cn) (>90%) mature into spheroids maintaining good cell viability. We further applied
Mingen Xu these acoustically assembled spheroids to drug testing to explore their potency in
(xumingen@hdu.edu.cn) drug response. In conclusion, this 3D acoustic cell assembly device may pave the way
Citation: Miao T, Chen K, Wei X, for the scale-up fabrication of cell spheroids or even organoids, to enable flexible
et al., 2023, High-throughput application in various biomedical applications, such as high-throughput screening,
fabrication of cell spheroids with 3D
acoustic assembly devices. disease modeling, tissue engineering, and regenerative medicine.
Int J Bioprint, 9(4): 733.
https://doi.org/10.18063/ijb.733
Keywords: Acoustic cell assembly; Levitated acoustic nodes; Cell spheroids; Drug
Received: February 20, 2023
Accepted: March 17, 2023 screening; High-throughput fabrication
Published Online: April 17, 2023
Copyright: © 2023 Author(s).
This is an Open Access article 1. Introduction
distributed under the terms of the
Creative Commons Attribution During the last decades, cell spheroids as advantageous models were used in various
License, permitting distribution,
[1]
[2]
and reproduction in any medium, biomedicine studies, such as drug screening , disease modeling , tissue engineering,
[3]
provided the original work is and regenerative medicine . Compared to commonly two-dimensional (2D)
properly cited. monolayer cultures, tumor spheroids represent better in vivo histological and biological
Publisher’s Note: Whioce characteristics, such as three-dimensional (3D) distribution of nutrients, metabolites
Publishing remains neutral with and oxygen, as well as complex interactions of cells and extracellular matrix , making
[4]
regard to jurisdictional claims in [5-7]
published maps and institutional their drug responses similar to those found in vivo . More recently, cell spheroids
affiliations. as building blocks promise to bring tissue engineering to next level [8-10] . Instead of

Volume 9 Issue 4 (2023) 261 https://doi.org/10.18063/ijb.733