11/7/2023 0 Comments Sequential circuits pro one 5530This limits their utility as in vitro models where patterns of cells and ECM are key aspects of development or the progression of disease. While spheroid cultures hold tremendous potential due to their organotypic cellular densities, it is difficult to control their patterning across larger length scales, to introduce the heterogeneity and resulting function of many tissues. For example, spheroid cultures have enabled the engineering of heart, liver, and lung fibrosis models 6, 15– 18, and high cell densities within spheroids result in oxygen gradients that mimic the cancer microenvironment 19– 21. High cell densities are necessary to accurately recapitulate many pathological disease states such as cancer or fibrosis where perturbed cell-cell and cell-ECM interactions are central to disease progression. Indeed, the organotypic cell densities in spheroids enhance the cell-cell and cell-extracellular matrix (ECM) interactions that are required to maintain cellular differentiation and phenotype, whereas these interactions are limited in traditional 2D cultures 11– 14. In these formats they are promising as drug screening platforms due to their superior predictability and physiological structure and function when compared to traditional monolayer cultures 7– 10. These spheroids are being used to emulate organs such as the intestine 2, liver 3, kidney 4, brain 5, and heart 6 to study human development and disease in vitro. 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.Ĭells possess the remarkable capacity to self-organize into multicellular spheroids in vitro, including from stem cells and into specialized organoid structures 1. 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. 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. 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. Current approaches are limited in the engineering of functional tissue models with requisite cell densities and heterogeneity to appropriately model cell and tissue behaviors. Cellular models are needed to study human development and disease in vitro, and to screen drugs for toxicity and efficacy.
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