Bio-Inspired Pancreas With Microfluidic Multi-Component Hydrogel Microfibers for Exploring Pancreatic Exocrine and Endocrine Interactions

Zhikun Huan , Zhiqiang Luo , Jingbo Li , Yunru Yu , Ling Li

Aggregate ›› 2025, Vol. 6 ›› Issue (12) : e70210

PDF
Aggregate ›› 2025, Vol. 6 ›› Issue (12) :e70210 DOI: 10.1002/agt2.70210
RESEARCH ARTICLE
Bio-Inspired Pancreas With Microfluidic Multi-Component Hydrogel Microfibers for Exploring Pancreatic Exocrine and Endocrine Interactions
Author information +
History +
PDF

Abstract

The rise in pancreatic diseases, resulting from improved living quality and lifestyle habits changes, has imposed a serious social burden. To better understand the pancreatic functions during disease progression, constructing a bionic pancreas is vital yet challenging in tissue engineering. Herein, inspired by the physiological anatomy of the pancreas, we introduce core-shell microfibers with pancreatic stellate cells (PSCs) in the shell and pancreatic β-cells in the core. Compared to traditional plate culture, the β-cells encapsulated in the microfiber exhibit enhanced glucose-stimulated insulin secretion. Such microfibers also serve as a platform to study the progression of diabetes of the exocrine pancreas, where the PSCs are activated under conditions of pancreatic exocrine diseases such as chronic pancreatitis. The activated PSCs impede insulin synthesis and increase apoptosis in β-cells, resulting in elevated blood glucose. This high-glucose microenvironment further exacerbates the activation of PSCs, causing a vicious cycle of diabetes. Additionally, the bio-inspired pancreas also demonstrates its potential in drug screening, as evidenced by testing the glucagon-like peptide 1 receptor agonist, Exendin-4. Building upon such features, it is convincing that these multi-component microfibers hold promise for exploring the pancreatic exocrine and endocrine interactions, and showing potential in disease modeling, drug screening, and regenerative medicine.

Keywords

cell encapsulation / microfluidics / microfiber / pancreas / tissue modeling

Cite this article

Download citation ▾
Zhikun Huan, Zhiqiang Luo, Jingbo Li, Yunru Yu, Ling Li. Bio-Inspired Pancreas With Microfluidic Multi-Component Hydrogel Microfibers for Exploring Pancreatic Exocrine and Endocrine Interactions. Aggregate, 2025, 6(12): e70210 DOI:10.1002/agt2.70210

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

O. E. Olaniru, U. Kadolsky, S. Kannambath, et al., “Single-cell Transcriptomic and Spatial Landscapes of the Developing human Pancreas,” Cell Metabolism 35 (2023): 184–199.e5.

[2]

Q. Zhou and D. A. Melton, “Pancreas Regeneration,” Nature 557 (2018): 351–358.

[3]

S. Haedersdal, A. Andersen, F. K. Knop, and T. Vilsboll, “Revisiting the Role of Glucagon in Health, Diabetes Mellitus and Other Metabolic Diseases,” Nature Reviews Endocrinology 19 (2023): 321–335.

[4]

J. E. Campbell and C. B. Newgard, “Mechanisms Controlling Pancreatic Islet Cell Function in Insulin Secretion,” Nature Reviews Molecular Cell Biology 22 (2021): 142–158.

[5]

K. J. Aney, W. J. Jeong, A. F. Vallejo, et al., “Novel Approach for Pancreas Transcriptomics Reveals the Cellular Landscape in Homeostasis and Acute Pancreatitis,” Gastroenterology 166 (2024): 1100–1113.

[6]

G. Malnassy, L. Ziolkowski, K. F. Macleod, and S. A. Oakes, “The Integrated Stress Response in Pancreatic Development, Tissue Homeostasis, and Cancer,” Gastroenterology 167 (2024): 1292–1306.

[7]

W. Jiang, L. Jin, D. Ju, et al., “The Pancreatic Clock Is a Key Determinant of Pancreatic Fibrosis Progression and Exocrine Dysfunction,” Science Translational Medicine 14 (2022): eabn3586.

[8]

S. M. Cohen and T. S. Kent, “Etiology, Diagnosis, and Modern Management of Chronic Pancreatitis,” JAMA Surgery 158 (2023): 652.

[9]

S. Misra, C. Ke, S. Srinivasan, et al., “Current Insights and Emerging Trends in Early-onset Type 2 Diabetes,” Lancet Diabetes & Endocrinology 11 (2023): 768–782.

[10]

J. Sun, J. Li, Z. Huan, et al., “Mesenchymal Stem Cell-Laden Composite β Cell Porous Microgel for Diabetes Treatment,” Advanced Functional Materials 33 (2023): 2211897.

[11]

J. Li, L. Sun, F. Bian, S. J. Pandol, and L. Li, “Emerging Approaches for the Development of Artificial Islets,” Smart Medicine 3 (2024): e20230042.

[12]

Z. Huan, J. Li, Z. Luo, Y. Yu, and L. Li, “Hydrogel-Encapsulated Pancreatic Islet Cells as a Promising Strategy for Diabetic Cell Therapy,” Research 7 (2024): 0403.

[13]

A. Fernandez, J. Casamitjana, A. Holguin-Horcajo, et al., “A Single-Cell Atlas of the Murine Pancreatic Ductal Tree Identifies Novel Cell Populations With Potential Implications in Pancreas Regeneration and Exocrine Pathogenesis,” Gastroenterology 167 (2024): 944–960.e15.

[14]

L. Huang, R. Desai, D. N. Conrad, et al., “Commitment and Oncogene-induced Plasticity of human Stem Cell-derived Pancreatic Acinar and Ductal Organoids,” Cell Stem Cell 28 (2021): 1090–1104.e6.

[15]

X. Lin, L. Sun, M. Lu, and Y. Zhao, “Biomimetic Gland Models With Engineered Stratagems,” Research 6 (2023): 0232.

[16]

T. L. Mastracci, M. Apte, L. T. Amundadottir, et al., “Integrated Physiology of the Exocrine and Endocrine Compartments in Pancreatic Diseases: Workshop Proceedings,” Diabetes 72 (2023): 433–448.

[17]

J. J. Wright, A. Eskaros, A. Windon, et al., “Exocrine Pancreas in Type 1 and Type 2 Diabetes: Different Patterns of Fibrosis, Metaplasia, Angiopathy, and Adiposity,” Diabetes 73 (2024): 1140–1152.

[18]

M. R. Rickels, A. W. Norris, and R. L. Hull, “A Tale of Two Pancreases: Exocrine Pathology and Endocrine Dysfunction,” Diabetologia 63 (2020): 2030–2039.

[19]

M. Slak Rupnik and M. Hara, “Local Dialogues Between the Endocrine and Exocrine Cells in the Pancreas,” Diabetes 73 (2024): 533–541.

[20]

H. Chen, J. Guo, F. Bian, and Y. Zhao, “Microfluidic Technologies for Cell Deformability Cytometry,” Smart Medicine 1 (2022): e20220001.

[21]

Y. Zhu, B. Kong, R. Liu, and Y. Zhao, “Developing Biomedical Engineering Technologies for Reproductive Medicine,” Smart Medicine 1 (2022): e20220006.

[22]

J. Wang, Y. Cheng, Y. Yu, et al., “Microfluidic Generation of Porous Microcarriers for Three-Dimensional Cell Culture,” ACS Applied Materials & Interfaces 7 (2015): 27035–27039.

[23]

Y. Yu, J. Guo, L. Sun, X. Zhang, and Y. Zhao, “Microfluidic Generation of Microsprings With Ionic Liquid Encapsulation for Flexible Electronics,” Research 2019 (2019): 6906275.

[24]

Y. Lei, Y. Wang, J. Shen, et al., “Injectable Hydrogel Microspheres With Self-renewable Hydration Layers Alleviate Osteoarthritis,” Science Advances 8 (2022): eabl6449.

[25]

C. Yang, Y. Yu, L. Shang, and Y. Zhao, “Flexible Hemline-shaped Microfibers for Liquid Transport,” Nature Chemical Engineering 1 (2024): 87–96.

[26]

X. Wang, K. G. Maxwell, K. Wang, et al., “A Nanofibrous Encapsulation Device for Safe Delivery of Insulin-producing Cells to Treat Type 1 Diabetes,” Science Translational Medicine 13 (2021): eabb4601.

[27]

X. Zhang, M. Lu, X. Cao, and Y. Zhao, “Functional Microneedles for Wearable Electronics,” Smart Medicine 2 (2023): e20220023.

[28]

H. Zhang, G. Chen, Y. Yu, J. Guo, Q. Tan, and Y. Zhao, “Microfluidic Printing of Slippery Textiles for Medical Drainage Around Wounds,” Advanced Science 7 (2020): 2000789.

[29]

Y. Cheng, F. Zheng, J. Lu, et al., “Bioinspired Multicompartmental Microfibers From Microfluidics,” Advanced Materials 26 (2014): 5184–5190.

[30]

Y. Yu, L. Shang, J. Guo, J. Wang, and Y. Zhao, “Design of Capillary Microfluidics for Spinning Cell-laden Microfibers,” Nature Protocols 13 (2018): 2557–2579.

[31]

L. Shang, Y. Yu, Y. Liu, Z. Chen, T. Kong, and Y. Zhao, “Spinning and Applications of Bioinspired Fiber Systems,” ACS Nano 13 (2019): 2749–2772.

[32]

J. Li, H. Zhang, L. Sun, et al., “Porous Microcarriers With Pancreatic β Cell Aggregates Loading for Diabetic Care,” Chemical Engineering Journal 436 (2022): 135174.

[33]

H. Onoe, T. Okitsu, A. Itou, et al., “Metre-long Cell-laden Microfibres Exhibit Tissue Morphologies and Functions,” Nature Materials 12 (2013): 584–590.

[34]

T. Watanabe, T. Okitsu, F. Ozawa, et al., “Millimeter-thick Xenoislet-laden Fibers as Retrievable Transplants Mitigate Foreign Body Reactions for Long-term Glycemic Control in Diabetic Mice,” Biomaterials 255 (2020): 120162.

[35]

J. Wang, D. Huang, H. Chen, and Y. Zhao, “Biomimetic Hepatic Lobules From Three-dimensional Imprinted Cell Sheets,” Scientific Bulletin 69 (2024): 1448–1457.

[36]

G. Chen, F. Wang, X. Zhang, Y. Shang, and Y. Zhao, “Living Microecological Hydrogels for Wound Healing,” Science Advances 9 (2023): eadg3478.

[37]

X. Lin, L. Cai, X. Cao, and Y. Zhao, “Stimuli-Responsive Silk Fibroin for on-Demand Drug Delivery,” Smart Medicine 2 (2023): e20220019.

[38]

Y. Peng, Y. Zhuang, Y. Liu, et al., “Bioinspired Gradient Scaffolds for Osteochondral Tissue Engineering,” Exploration 3 (2023): 20210043.

[39]

Y. Xu, Q. Saiding, X. Zhou, J. Wang, W. Cui, and X. Chen, “Electrospun fiber-Based Immune Engineering in Regenerative Medicine,” Smart Medicine 3 (2024): e20230034.

[40]

L. Wei, S. Wang, M. Shan, et al., “Conductive Fibers for Biomedical Applications,” Bioactive Materials 22 (2023): 343.

[41]

M. Filippi, T. Buchner, O. Yasa, S. Weirich, and R. K. Katzschmann, “Microfluidic Tissue Engineering and Bio-Actuation,” Advanced Materials 34 (2022): e2108427.

[42]

K. O. Rojek, M. Cwiklinska, J. Kuczak, and J. Guzowski, “Microfluidic Formulation of Topological Hydrogels for Microtissue Engineering,” Chemical Reviews 122 (2022): 16839–16909.

[43]

X. Wang, C. Yang, Y. Yu, and Y. Zhao, “In Situ 3D Bioprinting Living Photosynthetic Scaffolds for Autotrophic Wound Healing,” Research 2022 (2022): 9794745.

[44]

L. Sun, H. Chen, D. Xu, R. Liu, and Y. Zhao, “Developing organs-on-chips for Biomedical Applications,” Smart Medicine 3 (2024): e20240009.

[45]

J. Liu, Q. Song, W. Yin, et al., “Bioactive Scaffolds for Tissue Engineering: A Review of Decellularized Extracellular Matrix Applications and Innovations,” Exploration 5 (2025): 20230078.

[46]

N. Thierens, R. C. Verdonk, J. M. Lohr, H. C. van Santvoort, S. A. Bouwense, and J. E. van Hooft, “Chronic Pancreatitis,” Lancet 404 (2025): 2605–2618.

[47]

F. F. Li, B. J. Chen, W. Li, et al., “Islet Stellate Cells Isolated From Fibrotic Islet of Goto-Kakizaki Rats Affect Biological Behavior of Beta-Cell,” Journal of Diabetes Research 2016 (2016): 1–9.

[48]

Y. Zhou, J. Zhou, B. Sun, et al., “Vitamin A Deficiency Causes Islet Dysfunction by Inducing Islet Stellate Cell Activation via Cellular Retinol Binding Protein 1,” International Journal of Biology Sciences 16 (2020): 947–956.

[49]

D. An, A. Chiu, J. A. Flanders, et al., “Designing a Retrievable and Scalable Cell Encapsulation Device for Potential Treatment of Type 1 Diabetes,” Proceedings of the National Academy of Sciences of the United States of America 115 (2018): E263.

[50]

S. Ikeo, Y. Yamamoto, K. Ikeda, et al., “Core-shell Hydrogel Microfiber-expanded Pluripotent Stem Cell-derived Lung Progenitors Applicable to Lung Reconstruction in Vivo,” Biomaterials 276 (2021): 121031.

[51]

K. Yu, H. Huangfu, Q. Qin, et al., “Application of Bone Marrow-Derived Macrophages Combined With Bone Mesenchymal Stem Cells in Dual-Channel Three-Dimensional Bioprinting Scaffolds for Early Immune Regulation and Osteogenic Induction in Rat Calvarial Defects,” ACS Applied Materials & Interfaces 14 (2022): 47052–47065.

[52]

X. Wu, H. Zhu, J. Che, Y. Xu, Q. Tan, and Y. Zhao, “Stem Cell Niche-inspired Microcarriers With ADSCs Encapsulation for Diabetic Wound Treatment,” Bioactive Materials 26 (2023): 159.

[53]

A. Masamune, T. Watanabe, K. Kikuta, K. Satoh, and T. Shimosegawa, “NADPH Oxidase Plays a Crucial Role in the Activation of Pancreatic Stellate Cells,” American Journal of Physiology Gastrointestinal and Liver Physiology 294 (2008): G99–G108.

[54]

S. M. Swain, J. M. Romac, S. R. Vigna, and R. A. Liddle, “Piezo1-mediated Stellate Cell Activation Causes Pressure-induced Pancreatic Fibrosis in Mice,” JCI Insight 7 (2022): e158288.

[55]

A. Masamune, K. Kikuta, M. Satoh, K. Satoh, and T. Shimosegawa, “Rho Kinase Inhibitors Block Activation of Pancreatic Stellate Cells,” British Journal of Pharmacology 140 (2003): 1292–1302.

[56]

S. Ueberberg, M. A. Nauck, W. Uhl, et al., “Islet Amyloid in Patients With Diabetes due to Exocrine Pancreatic Disorders, Type 2 Diabetes, and Nondiabetic Patients,” Journal of Clinical Endocrinology and Metabolism (2020): 105.

[57]

J. A. Emamaullee and A. M. Shapiro, “Interventional Strategies to Prevent β-Cell Apoptosis in Islet Transplantation,” Diabetes 55 (2006): 1907–1914.

[58]

J. Li, R. Inoue, Y. Togashi, et al., “Imeglimin Ameliorates β-Cell Apoptosis by Modulating the Endoplasmic Reticulum Homeostasis Pathway,” Diabetes 71 (2022): 424–439.

[59]

W. Ahmad, B. Ijaz, K. Shabbiri, F. Ahmed, and S. Rehman, “Oxidative Toxicity in Diabetes and Alzheimer's Disease: Mechanisms Behind ROS/ RNS Generation,” Journal of Biomedical Science 24 (2017): 76.

[60]

D. S. Kim and P. E. Scherer, “Obesity, Diabetes, and Increased Cancer Progression,” Diabetes & Metabolism Journal 45 (2021): 799–812.

[61]

F. Kong, Y. Pan, and D. Wu, “Activation and Regulation of Pancreatic Stellate Cells in Chronic Pancreatic Fibrosis: A Potential Therapeutic Approach for Chronic Pancreatitis,” Biomedicines 12 (2024): 108.

[62]

N. Tanday, P. R. Flatt, and N. Irwin, “Metabolic Responses and Benefits of Glucagon-Like Peptide-1 (GLP-1) Receptor Ligands,” British Journal of Pharmacology 179 (2022): 526–541.

[63]

J. W. Kim, S. Y. Park, Y. H. You, et al., “Suppression of ROS Production by Exendin-4 in PSC Attenuates the High Glucose-Induced Islet Fibrosis,” PLoS ONE 11 (2016): e0163187.

[64]

T. Nakamura, T. Ito, M. Uchida, et al., “PSCs and GLP-1R: Occurrence in Normal Pancreas, Acute/Chronic Pancreatitis and Effect of Their Activation by a GLP-1R Agonist,” Laboratory Investigation 94 (2014): 63–78.

[65]

T. Tomono, H. Yagi, M. Ukawa, et al., “Nasal Absorption Enhancement of Protein Drugs Independent to Their Chemical Properties in the Presence of Hyaluronic Acid Modified With Tetraglycine-L-octaarginine,” European Journal of Pharmaceutics and Biopharmaceutics 154 (2020): 186–194.

RIGHTS & PERMISSIONS

2025 The Author(s). Aggregate published by SCUT, AIEI, and John Wiley & Sons Australia, Ltd.

PDF

7

Accesses

0

Citation

Detail

Sections
Recommended

/