Page 9 - IJB-9-3

International Journal of Bioprinting

RESEARCH ARTICLE
Bioprinting of hydrogel beads to engineer

pancreatic tumor-stroma microtissues for drug
screening

1†
1†
1,2
1
1,2
Beisi Huang , Xiaoyun Wei *, Keke Chen , Ling Wang *, Mingen Xu *
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
(This article belongs to the Special Issue: Advances in 3D bioprinting for regenerative medicine
and drug screening)

Abstract

Pancreatic ductal adenocarcinoma (PDAC) having features of dense fibrotic stromal and
extracellular matrix (ECM) components has poor clinical outcome. In vitro construction
of relevant preclinical PDAC models recapitulating the tumor-stroma characteristics is
therefore in great need for the development of pancreatic cancer therapy. In this work,
a three-dimensional (3D) heterogeneous PDAC microtissue based on a dot extrusion
† These authors contributed equally printing (DEP) system is reported. Gelatin methacryloyl (GelMA) hydrogel beads
to this work. encapsulating human pancreatic cancer cells and stromal fibroblasts were printed,
*Corresponding authors: which demonstrated the capacity of providing ECM-mimetic microenvironments
Xiaoyun Wei and thus mimicked the native cell-cell junctions and cell-ECM interactions. Besides,
(wxyun@hdu.edu.cn) the spherical structure of the generated hydrogel beads, which took the advantage
Ling Wang
(lingw@hdu.edu.cn) of encapsulating cells in a reduced volume, enabled efficient diffusion of oxygen,
Mingen Xu nutrients and cell waste, thus allowing the embedded cells to proliferate and eventually
(xumingen@hdu.edu.cn) form a dense pancreatic tumor-stroma microtissue around hundred microns.
Citation: Huang B, Wei X, Chen K, Furthermore, a tunable stromal microenvironment was easily achieved by adjusting
et al., 2023, Bioprinting of hydrogel the density of stromal cells in the hydrogel beads. Based on our results, the produced
beads to engineer pancreatic
tumor-stroma microtissues for drug heterogeneous pancreatic microtissue recapitulated the features of cellular interactions
screening. Int J Bioprint, 9(3): 676. and stromal-like microenvironments, and displayed better anti-cancer drug resistance
https://doi.org/10.18063/ijb.676 than mono-cultured pancreatic cancer spheroids. Together, the DEP system possesses
Received: August 31, 2022 the ability to simply and flexibly produce GelMA hydrogel beads, providing a robust
manufacturing tool for the pancreatic cancer drug screening platform fabrication. In
Accepted: November 22, 2022
addition, the engineered pancreatic tumor-stroma microtissue based on bioprinted
Published Online: February 01, 2023 GelMA hydrogel beads, other than being ECM-biomimetic and stroma-tunable, can
Copyright: © 2023 Author(s). be used for observation in situ and may serve as a new drug screening platform.
This is an Open Access article
distributed under the terms of the
Creative Commons Attribution Keywords: 3D bioprinting; GelMA hydrogel beads; Tumor-stroma microtissues; Tunable
License, permitting distribution, stromal microenvironment; Drug screening
and reproduction in any medium,
provided the original work is
properly cited.
Publisher’s Note: Whioce
Publishing remains neutral with 1. Introduction
regard to jurisdictional claims in
published maps and institutional Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with an
affiliations. escalating trend of mortality rate [1,2] . As reported, PDAC progresses rapidly and has a

Volume 9 Issue 3 (2023) 1 https://doi.org/10.18063/ijb.v9i3.676