High-throughput bioprinting of spheroids for scalable tissue fabrication

Myoung Hwan Kim, Yogendra Pratap Singh, Nazmiye Celik, Miji Yeo, Elias Rizk, Daniel J. Hayes and Ibrahim T. Ozbolat ()
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Myoung Hwan Kim: Penn State University
Yogendra Pratap Singh: Penn State University
Nazmiye Celik: Penn State University
Miji Yeo: Penn State University
Elias Rizk: Penn State Milton S. Hershey Medical Center
Daniel J. Hayes: Penn State University
Ibrahim T. Ozbolat: Penn State University

Nature Communications, 2024, vol. 15, issue 1, 1-21

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-54504-7

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