AccScience Publishing / IJB / Online First / DOI: 10.36922/IJB025360368
RESEARCH ARTICLE
Early Access

Bioprinting functional human islet tissue models with vascular elements by aggregate-based co-culture and self-assembly

Yijun Su1,2† Supeng Ding3† Tiankun Liu2 Yongyong Zhou2 Yinying Lu1,2 Feng Lin1 Mingen Xu4* Rui Yao1,2,5*
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1 Biomanufacturing and Rapid Forming Technology Key Laboratory of Beijing, Department of Mechanical Engineering, Tsinghua University, Beijing 100084, China
2 Human Organ Physiopathology Emulation System, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
3 Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD 21218, USA
4 Key Laboratory of Medical Information and 3D Bioprinting of Zhejiang Province, Hangzhou Dianzi University, Hangzhou 310018, China
5 Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China
†These authors contributed equally to this work.
Received: 6 September 2025 | Accepted: 2 October 2025 | Published online: 7 October 2025
(This article belongs to the Special Issue 3D Bioprinting and Stem Cells for Human Tissue Reconstruction)
© 2025 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 ( https://creativecommons.org/licenses/by/4.0/ )
Abstract

Diabetes is a severe metabolic disease worldwide. Current treatments, including islet/pancreas transplantation and insulin therapy, are limited by donor shortages and incomplete glycaemic control. Islet organoids, three-dimensional (3D) cell aggregates that mimic pancreatic islets, offer a powerful tool for diabetes research, drug screening, and transplantation therapies. However, challenges remain in engineering methods for the scalable preparation of human islet organoids (hIOs) with homogeneous consistency and controllable incorporation of vascular elements. Here, we develop a novel bioengineering approach for the stable production of human islet tissue models with vascular elements using 3D bioprinting-based organoid co-culture and cell self-assembly principles. Human adipose-derived mesenchymal stem cells are differentiated into massive and uniform human islet β-like cell aggregates (hICAs) by an off-the-shelf polydimethylsiloxane user-defined micropatterning platform system. A tri-module thermal-controlled bioprinting process employing a gelatin/alginate/matrigel bioink is used for the 3D bioprinting of hICAs and human umbilical vein endothelial cells (HUVECs). Compared with bioprinting of solely hICAs, co-bioprinting and co-culture of hICAs and HUVECs demonstrate morphogenesis recapitulating human islet development, significantly upregulated gene expression of pancreatic islet-related and endothelial cell-related markers, and islet function, i.e., glucose-stimulated insulin secretion. Thus, the self-assembly of hICAs and HUVECs for forming hIOs with vascular elements mimics natural human pancreatic islets and may promote functional maturity. Our method provides a scalable platform for generating vascularized aggregation-based tissue models, supporting studies of pancreatic development and diabetes therapy.

Keywords
Human islet tissue models
Bioprinting
Islet β-like cell aggregates
Human adipose-derived mesenchymal stem cells
Funding
This work was supported by funding from the National Key Research and Development Program of China (2022YFA1104600, 2018YFA0109000).
Conflict of interest
The authors declare no conflict of interest.
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International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing