High-throughput bioprinting of spheroids for scalable tissue fabrication
Myoung Hwan Kim, Yogendra Pratap Singh, Nazmiye Celik, Miji Yeo, Elias Rizk, Daniel J. Hayes, İbrahim T. Özbolat
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. HITS-Bio, a high-throughput bioprinting platform, rapidly assembles spheroids to mimic native tissue architecture. Its intraoperative application in bone shows near-complete calvarial defect repair in rats and fabrication of scalable cartilage.