01948nas a2200277   4500000000100000000000100001008004100002260001500043653002700058653002700085653002600112653002300138100002000161700002600181700001800207700001300225700001500238700002000253700002300273245007700296856005500373300001000428490000700438520121100445022001401656       2024                            d  c2024-11-2110aBiomaterials – cells10aMesenchymal stem cells10aRegenerative Medicine10aTissue engineering1 aMyoung Hwan Kim1 aYogendra Pratap Singh1 aNazmiye Celik1 aMiji Yeo1 aElias Rizk1 aDaniel J. Hayes1 aIbrahim T. Ozbolat00aHigh-throughput bioprinting of spheroids for scalable tissue fabrication  uhttps://www.nature.com/articles/s41467-024-54504-7  a100830 v153 aTissue 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.  a2041-1723