02040nas a2200241   4500000000100000000000100001008004100002260001500043653002700058653002800085653002600113653001800139653001900157100001900176700002400195700002100219245012200240856005500362300000800417490000700425520135200432022001401784       2021                            d  c2021-02-0210aBiomedical Engineering10aCardiovascular Diseases10aCardiovascular models10aDrug delivery10aDrug screening1 aAndrew C. Daly1 aMatthew D. Davidson1 aJason A. Burdick00a3D bioprinting of high cell-density heterogeneous tissue models through spheroid fusion within self-healing hydrogels  uhttps://www.nature.com/articles/s41467-021-21029-2  a7530 v123 aCellular 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.  a2041-1723