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Sacrificial microgel-laden bioink-enabled 3D bioprinting of mesoscale pore networks

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Abstract

Three-dimensional (3D) bioprinting is a powerful approach that enables the fabrication of 3D tissue constructs that retain complex biological functions. However, the dense hydrogel networks that form after the gelation of bioinks often restrict the migration and proliferation of encapsulated cells. Herein, a sacrificial microgel-laden bioink strategy was designed for directly bioprinting constructs with mesoscale pore networks (MPNs) for enhancing nutrient delivery and cell growth. The sacrificial microgel-laden bioink, which contains cell/gelatin methacryloyl (GelMA) mixture and gelled gelatin microgel, is first thermo-crosslinked to fabricate temporary predesigned cell-laden constructs by extrusion bioprinting onto a cold platform. Then, the construct is permanently stabilized through photo-crosslinking of GelMA. The MPNs inside the printed constructs are formed after subsequent dissolution of the gelatin microgel. These MPNs allowed for effective oxygen/nutrient diffusion, facilitating the generation of bioactive tissues. Specifically, osteoblast and human umbilical vein endothelial cells encapsulated in the bioprinted large-scale constructs (≥ 1 cm) with MPNs showed enhanced bioactivity during culture. The 3D bioprinting strategy based on the sacrificial microgel-laden bioink provided a facile method to facilitate formation of complex tissue constructs with MPNs and set a foundation for future optimization of MPN-based tissue constructs with applications in diverse areas of tissue engineering.

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Acknowledgements

This work was sponsored by the National Nature Science Foundation of China (Nos. U1609207, 81827804).

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Authors and Affiliations

  1. State Key Laboratory of Fluid Power and Mechatronic Systems, College of Mechanical Engineering, Zhejiang University, Hangzhou, 310027, China

    Lei Shao, Qing Gao, Chaoqi Xie, Jianzhong Fu & Yong He

  2. Key Laboratory of 3D Printing Process and Equipment of Zhejiang Province, College of Mechanical Engineering, Zhejiang University, Hangzhou, 310027, China

    Lei Shao, Qing Gao, Chaoqi Xie, Jianzhong Fu & Yong He

  3. Department of Cardiology, The Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, 310009, China

    Meixiang Xiang

  4. Department of Vascular Surgery, The Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, 310009, China

    Zhenjie Liu

  5. Zhejiang University Hospital, Zhejiang University, Hangzhou, 310027, Zhejiang, China

    Liulin Xiang

  6. Key Laboratory of Materials Processing and Mold, Zhengzhou University, Zhengzhou, 450002, China

    Yong He

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  1. Lei Shao
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  2. Qing Gao
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  3. Chaoqi Xie
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  6. Zhenjie Liu
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  8. Yong He
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Correspondence to Qing Gao, Zhenjie Liu or Yong He.

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Shao, L., Gao, Q., Xie, C. et al. Sacrificial microgel-laden bioink-enabled 3D bioprinting of mesoscale pore networks. Bio-des. Manuf. 3, 30–39 (2020). https://doi.org/10.1007/s42242-020-00062-y

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  • DOI: https://doi.org/10.1007/s42242-020-00062-y

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