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3D bioprinting of high cell-density heterogeneous tissue models through spheroid fusion within self-healing hydrogels

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  • Andrew C. Daly

    (University of Pennsylvania)

  • Matthew D. Davidson

    (University of Pennsylvania)

  • Jason A. Burdick

    (University of Pennsylvania)

Abstract

Cellular models are needed to study human development and disease in vitro, and to screen drugs for toxicity and efficacy. Current approaches are limited in the engineering of functional tissue models with requisite cell densities and heterogeneity to appropriately model cell and tissue behaviors. Here, we develop a bioprinting approach to transfer spheroids into self-healing support hydrogels at high resolution, which enables their patterning and fusion into high-cell density microtissues of prescribed spatial organization. As an example application, we bioprint induced pluripotent stem cell-derived cardiac microtissue models with spatially controlled cardiomyocyte and fibroblast cell ratios to replicate the structural and functional features of scarred cardiac tissue that arise following myocardial infarction, including reduced contractility and irregular electrical activity. The bioprinted in vitro model is combined with functional readouts to probe how various pro-regenerative microRNA treatment regimes influence tissue regeneration and recovery of function as a result of cardiomyocyte proliferation. This method is useful for a range of biomedical applications, including the development of precision models to mimic diseases and the screening of drugs, particularly where high cell densities and heterogeneity are important.

Suggested Citation

  • Andrew C. Daly & Matthew D. Davidson & Jason A. Burdick, 2021. "3D bioprinting of high cell-density heterogeneous tissue models through spheroid fusion within self-healing hydrogels," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21029-2
    DOI: 10.1038/s41467-021-21029-2
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    Cited by:

    1. Yanmei Zhang & Qifan Hu & Yuquan Pei & Hao Luo & Zixuan Wang & Xinxin Xu & Qing Zhang & Jianli Dai & Qianqian Wang & Zilian Fan & Yongcong Fang & Min Ye & Binhan Li & Mailin Chen & Qi Xue & Qingfeng Z, 2024. "A patient-specific lung cancer assembloid model with heterogeneous tumor microenvironments," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    2. Sungjin Min & Suran Kim & Woo-Sup Sim & Yi Sun Choi & Hyebin Joo & Jae-Hyun Park & Su-Jin Lee & Hyeok Kim & Mi Jeong Lee & Inhea Jeong & Baofang Cui & Sung-Hyun Jo & Jin-Ju Kim & Seok Beom Hong & Yeon, 2024. "Versatile human cardiac tissues engineered with perfusable heart extracellular microenvironment for biomedical applications," Nature Communications, Nature, vol. 15(1), pages 1-22, December.
    3. Yangteng Ou & Shixiang Cao & Yang Zhang & Hongjia Zhu & Chengzhi Guo & Wei Yan & Fengxue Xin & Weiliang Dong & Yanli Zhang & Masashi Narita & Ziyi Yu & Tuomas P. J. Knowles, 2023. "Bioprinting microporous functional living materials from protein-based core-shell microgels," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    4. Julien G. Roth & Lucia G. Brunel & Michelle S. Huang & Yueming Liu & Betty Cai & Sauradeep Sinha & Fan Yang & Sergiu P. Pașca & Sungchul Shin & Sarah C. Heilshorn, 2023. "Spatially controlled construction of assembloids using bioprinting," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    5. Yuanxiong Cao & Jiayi Tan & Haoran Zhao & Ting Deng & Yunxia Hu & Junhong Zeng & Jiawei Li & Yifan Cheng & Jiyuan Tang & Zhiwei Hu & Keer Hu & Bing Xu & Zitian Wang & Yaojiong Wu & Peter E. Lobie & Sh, 2022. "Bead-jet printing enabled sparse mesenchymal stem cell patterning augments skeletal muscle and hair follicle regeneration," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    6. Matthew A. Heinrich & Ricard Alert & Abraham E. Wolf & Andrej Košmrlj & Daniel J. Cohen, 2022. "Self-assembly of tessellated tissue sheets by expansion and collision," Nature Communications, Nature, vol. 13(1), pages 1-10, December.

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