AccScience Publishing / IJB / Online First / DOI: 10.36922/ijb.2874

Effect of tunable stiffness on immune responses in 3D-bioprinted alginate–gelatin scaffolds

Qinghua Liu1 Yu Feng1 Bin Yao1 Zhao Li1 Yi Kong1 Chao Zhang1 Yaxin Tan1 Wei Song1 Jirigala Enhe2 Xiaohe Li2* Sha Huang1*
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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
Submitted: 2 February 2024 | Accepted: 27 February 2024 | Published: 3 April 2024
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( )

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 scaffolds and assessed the immune responses they provoked both in vitro and in vivo. Our results revealed that higher-stiffness implants could drive macrophage polarization toward pro-inflammatory phenotypes in vivo. Furthermore, our animal experiments demonstrated that high-stiffness hydrogels elicited elevated immune responses through the TLR4/Myd88/NF-κB signaling pathway and IL-6/JAK-STAT signaling pathway. Collectively, our study demonstrates that increased implant stiffness correlates with stronger immune responses. These findings are expected to provide novel insights for the clinical application of alginate–gelatin composite hydrogels.

3D bioprinting
Tunable stiffness
Alginate–gelatin scaffolds
Immune responses
This study was supported by the National Natural Science Foundation of China (32000969, 82274362), National Key Research and Development Program of China (2022YFA1104600, 2022YFA1104604), Beijing Natural Science Foundation (L234066), Natural Science Foundation of Inner Mongolia Autonomous Region of China (2021LHMS08050), Inner Mongolia Autonomous Region Higher Education Innovation Team Development Plan (NMGIRT2227), Inner Mongolia Youth Science and Technology Talent support program (NJYT24031), Key Project of Inner Mongolia Medical University (YKD2021ZD001), Youth Independent Innovation Science Fund Project of PLA General Hospital (22QNFC018), Ulanqab Basic Research Project (2021JC321), and Inner Mongolia Medical University Doctoral Initiation Program (YKD2023BSQD012).
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Conflict of interest
The authors declare no conflicts of interest.
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International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing