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High-throughput bioprinting of spheroids for scalable tissue fabrication

Author

Listed:
  • Myoung Hwan Kim

    (Penn State University
    Penn State University)

  • Yogendra Pratap Singh

    (Penn State University
    Penn State University)

  • Nazmiye Celik

    (Penn State University
    Penn State University)

  • Miji Yeo

    (Penn State University
    Penn State University)

  • Elias Rizk

    (Penn State Milton S. Hershey Medical Center)

  • Daniel J. Hayes

    (Penn State University
    Penn State University
    Penn State University)

  • Ibrahim T. Ozbolat

    (Penn State University
    Penn State University
    Penn State University
    Penn State Milton S. Hershey Medical Center)

Abstract

Tissue biofabrication mimicking organ-specific architecture and function requires physiologically-relevant cell densities. Bioprinting using spheroids can achieve this, but is limited due to the lack of practical, scalable techniques. This study presents HITS-Bio (High-throughput Integrated Tissue Fabrication System for Bioprinting), a multiarray bioprinting technique for rapidly positioning multiple spheroids simultaneously using a digitally-controlled nozzle array (DCNA). HITS-Bio achieves an unprecedented speed, ten times faster compared to existing techniques while maintaining high cell viability ( > 90%). The utility of HITS-Bio was exemplified in multiple applications, including intraoperative bioprinting with microRNA transfected human adipose-derived stem cell spheroids for calvarial bone regeneration ( ~ 30 mm3) in a rat model achieving a near-complete defect closure (bone coverage area of ~ 91% in 3 weeks and ~96% in 6 weeks). Additionally, the successful fabrication of scalable cartilage constructs (1 cm3) containing ~600 chondrogenic spheroids highlights its high-throughput efficiency (under 40 min per construct) and potential for repairing volumetric defects.

Suggested Citation

  • Myoung Hwan Kim & Yogendra Pratap Singh & Nazmiye Celik & Miji Yeo & Elias Rizk & Daniel J. Hayes & Ibrahim T. Ozbolat, 2024. "High-throughput bioprinting of spheroids for scalable tissue fabrication," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-54504-7
    DOI: 10.1038/s41467-024-54504-7
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    References listed on IDEAS

    as
    1. 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.
    2. Mark A. Skylar-Scott & Jochen Mueller & Claas W. Visser & Jennifer A. Lewis, 2019. "Voxelated soft matter via multimaterial multinozzle 3D printing," Nature, Nature, vol. 575(7782), pages 330-335, November.
    3. 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.
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