Page 345 - IJB-10-4

International

Journal of Bioprinting

RESEARCH ARTICLE
Effect of tunable stiffness on immune responses

in 3D-bioprinted alginate–gelatin scaffolds

Qinghua Liu , Yu Feng , Bin Yao , Zhao Li , Yi Kong , Chao Zhang , Yaxin Tan ,
1†
1
1†
1†
1
1
1
Wei Song , Jirigala Enhe , Xiaohe Li *, and Sha Huang *
1
1
2
2
1 Research Center for Tissue Repair and Regeneration affiliated to the Medical Innovation Research
Department, PLA General Hospital and PLA Medical College, Beijing, China
2 Department of Anatomy the Basic Medicine College, Inner Mongolia Medical University, Hohhot,
Inner Mongolia, China
Abstract
Tissue engineering is an approach used to restore damaged tissues and organs
using biomaterials that support cell adhesion, growth, and proliferation. However,
immune responses triggered by tissue injury and biomaterial implantation can
lead to undesired reactions such as foreign body response and fibrotic capsule
formation. Macrophages play a critical role in these immune responses. Therefore,
comprehending and controlling the immune responses to biomaterials are crucial
for successful clinical translation in tissue engineering. In this experimental study, we
fabricated three-dimensional-bioprinted hydrogel scaffolds with adaptable stiffness
by adjusting the alginate–gelatin ratio. We examined the physical properties of these
† These authors contributed equally scaffolds and assessed the immune responses they provoked both in vitro and in
to this work.
vivo. Our results revealed that higher-stiffness implants could drive macrophage
*Corresponding authors: polarization toward pro-inflammatory phenotypes in vivo. Furthermore, our animal
Sha Huang
(stellarahuang@sina.com) experiments demonstrated that high-stiffness hydrogels elicited elevated immune
Xiaohe Li responses through the TLR4/Myd88/NF-κB signaling pathway and IL-6/JAK-STAT
(798242742@qq.com) signaling pathway. Collectively, our study demonstrates that increased implant
stiffness correlates with stronger immune responses. These findings are expected
Citation: Liu Q, Feng Y, Yao B,
et al. Effect of tunable stiffness on to provide novel insights for the clinical application of alginate–gelatin composite
immune responses in 3D-bioprinted hydrogels.
alginate–gelatin scaffolds.
Int J Bioprint. 2024;10(4):2874.
doi: 10.36922/ijb.2874 Keywords: 3D bioprinting; Tunable stiffness; Alginate–gelatin scaffolds;
Received: February 2, 2024 Immune responses
Accepted: February 27, 2024
Published Online: April 3, 2024
Copyright: © 2024 Author(s).
This is an Open Access article 1. Introduction
distributed under the terms of the
Creative Commons Attribution Tissue engineering is an approach used to repair damaged tissues and organs by utilizing
License, permitting distribution,
and reproduction in any medium, biocompatible and degradable biomaterials that provide support for cell adhesion, growth,
provided the original work is and proliferation. Macrophages play a crucial role in the immune response triggered
1,2
properly cited. by tissue injury and biomaterial implantation. These tissue-resident macrophages are
3,4
Publisher’s Note: AccScience present in various tissues and are recruited to the site of injury in response to changes in the
Publishing remains neutral with microenvironment. During the acute inflammatory phase, macrophages transform into
5,6
regard to jurisdictional claims in
published maps and institutional a pro-inflammatory phenotype known as “M1 macrophages” in the presence of cytokines
7
affiliations. like interferon-γ (IFN-γ) and lipopolysaccharides (LPS). M1 macrophages regulate the
Volume 10 Issue 4 (2024) 337 doi: 10.36922/ijb.2874