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  2. Alginate-gelatin hydrogel scaffolds for establishing physiological barriers on a gut-brain-axis microchip

Alginate-gelatin hydrogel scaffolds for establishing physiological barriers on a gut-brain-axis microchip

  • Int J Biol Macromol. 2025 Jun:312:144084. doi: 10.1016/j.ijbiomac.2025.144084.
Gaowa Xing 1 Yuxuan Li 2 Zengnan Wu 2 Yuting Shang 2 Hongren Yao 2 Yanwei Jia 3 Jin-Ming Lin 4
Affiliations

Affiliations

  • 1 Key Laboratory of Ecology-Toxicological Effects and Control for Emerging Contaminants of Fujian Province, Key Laboratory of Ecological Environment and Information Atlas (Putian University) Fujian Provincial University, College of Environmental & Biological Engineering, Putian University, Putian 351100, China; Department of Chemistry, Beijing Key Laboratory of Microanalytical Methods and Instrumentation, Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Tsinghua University, Beijing 100084, China; State Key Laboratory of Analog and Mixed-Signal VLSI, Institute of Microelectronics, Faculty of Science and Technology, MoE Frontiers Science Center for Precision Oncology, University of Macau, Macau.
  • 2 Department of Chemistry, Beijing Key Laboratory of Microanalytical Methods and Instrumentation, Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Tsinghua University, Beijing 100084, China.
  • 3 State Key Laboratory of Analog and Mixed-Signal VLSI, Institute of Microelectronics, Faculty of Science and Technology, MoE Frontiers Science Center for Precision Oncology, University of Macau, Macau. Electronic address: yanweijia@um.edu.mo.
  • 4 Department of Chemistry, Beijing Key Laboratory of Microanalytical Methods and Instrumentation, Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Tsinghua University, Beijing 100084, China. Electronic address: jmlin@mail.tsinghua.edu.cn.
Abstract

Organ-on-chips (OOCs) technique has transferred real animal models to the in vitro models, especially for the exploration of the gut-brain-axis. In this work, we proposed a novel hydrogel-based microchip system to simulate two of the most indispensable physiological barriers in the gut-brain-axis, providing a feasible tool for studying the bacteria-induced regulations of tryptophan metabolism on cells. Using UV-light-induced hydrogel of alginate-gelatin mixture filled within the microchip as the cell scaffold, different cell layers were successfully inoculated and formed an intestinal barrier (IB) and a blood-brain barrier (BBB) with specific morphology and fundamental functions. Tryptophan-kynurenine pathway, a significant metabolic process in the gut-brain-axis, has been analyzed using this model by liquid chromatography-mass spectrometry and presented a possible explanation of this metabolic mechanism. Under Bacterial conditions, the tryptophan in IB was about 1.46 times higher than that in BBB, while this value was about 3.14 times higher for kynurenine, indicating that the BBB has selective permeability to tryptophan and hinders the diffusion of kynurenine. This alginate-gelatin hydrogel scaffold based OOCs system has successfully simulated the dual barriers without moral dilemmas of animal models and analyzed tryptophan metabolism among different physiological barriers, providing an important tool for simulating physiological models with multi-barrier structures.

Keywords

Alginate-gelatin hydrogel scaffolds; Blood-brain barrier; Intestinal barrier; Organ-on-chip; Tryptophan metabolism.

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