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Dissolvable temporary barrier: a novel paradigm for flexible hydrogel patterning in organ-on-a-chip models

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Abstract

A combination of hydrogels and microfluidics allows the construction of biomimetic three-dimensional (3D) tissue models in vitro, which are also known as organ-on-a-chip models. The hydrogel patterning with a well-controlled spatial distribution is typically achieved by embedding sophisticated microstructures to act as a boundary. However, these physical barriers inevitably expose cells/tissues to a less physiologically relevant microenvironment than in vivo conditions. Herein, we present a novel dissolvable temporary barrier (DTB) strategy that allows robust and flexible hydrogel patterning with great freedom of design and desirable flow stimuli for cellular hydrogels. The key aspect of this approach is the patterning of a water-soluble rigid barrier as a guiding path for the hydrogel using stencil printing technology, followed by a barrier-free medium perfusion after the dissolution of the DTB. Single and multiple tissue compartments with different geometries can be established using either straight or curved DTB structures. The effectiveness of this strategy is further validated by generating a 3D vascular network through vasculogenesis and angiogenesis using a vascularized microtumor model. As a new proof-of-concept in vasculature-on-a-chip, DTB enables seamless contact between the hydrogel and the culture medium in closed microdevices, which is an improved protocol for the fabrication of multiorgan chips. Therefore, we expect it to serve as a promising paradigm for organ-on-a-chip devices for the development of tumor vascularization and drug evaluation in the future preclinical studies.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (Nos. 31972929 and 62231025), the Research Program of Shanghai Science and Technology Committee (Nos. 21140901300 and 20DZ2220400), the Natural Science Foundation of Chongqing, China (No. CSTB2022NSCQ-MSX0767), the Interdisciplinary Program of Shanghai Jiao Tong University (Nos. YG2021ZD22 and YG2023LC04), the Foundation of National Center for Translational Medicine (Shanghai) SHU Branch (No. SUITM-2023008), and the Cross-disciplinary Research Fund of Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine (No. JYJC202108). The authors were also grateful to the Center for Advanced Electronic Materials and Devices (AEMD) of Shanghai Jiao Tong University.

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Authors and Affiliations

  1. Department of Micro/Nano Electronics, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China

    Ding Wang, Chenyang Zhou, Zhangjie Li, Kangyi Lu, Yijun Liu & Xiaolin Wang

  2. Department of Ophthalmology, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, 999077, China

    Qinyu Li

  3. Institute of Medical Robotics, Shanghai Jiao Tong University, Shanghai, 200240, China

    Lian Xuan & Xiaolin Wang

  4. National Key Laboratory of Advanced Micro and Nano Manufacture Technology, Shanghai Jiao Tong University, Shanghai, 200240, China

    Xiaolin Wang

  5. National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai, 200444, China

    Xiaolin Wang

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  1. Ding Wang
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Contributions

DW and QYL were involved in conceptualization, investigation, methodology, writing—original draft, and visualization; CYZ, ZJL, KYL, YJL, and LX helped in resources and writing—review and editing; XLW contributed to supervision and funding acquisition.

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Correspondence to Xiaolin Wang.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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Ding Wang and Qinyu Li have contributed equally to this work.

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Wang, D., Li, Q., Zhou, C. et al. Dissolvable temporary barrier: a novel paradigm for flexible hydrogel patterning in organ-on-a-chip models. Bio-des. Manuf. 7, 153–166 (2024). https://doi.org/10.1007/s42242-023-00267-x

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