3D-Engineered Organoids for Modelling Tissue Development and Precision Medicine

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About this Research Topic

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Background

In vitro tissue engineering enables the creation of reliable disease models as well as novel therapeutic testing approaches. To this date, there are several models for the engineering of human tissue with different degrees of complexity; there are 3D organoids, there are assembloids as a product of combining different organoid types, and 3D tissue engineered miniaturized constructs, which are created by integrating one or more cell types and a scaffold, therefore more complex models.

By recreating many of the cell-cell and cell-matrix interactions found in native tissues, as well as providing the proper biophysical and biochemical stimuli to cells mimicking the in vivo microenvironment, these models provide more physiologically accurate models than traditional 2D or monolayer cultures, which can be used as a successful replacement for animal models by pharmaceutical companies.

There have been several significant advances in the engineering of 3D organoids: the integration of different cell types with natural or artificial supports, functionalized gels and decellularized organs, and the tuning of biomechanical and biochemical stimuli. Nonetheless, the effective translation of these models for drug screening and the complete replacement of animal models remains a challenge.

Tackling the current challenges in this context will require additional efforts to: a) improve the spatiotemporal control of cellular organization and their function, b) maximize the outcome of 3D systems and c) Standardize media formulation for maintaining the survival and function of multiple cell types. The ability to control evolution/development over time would be a significant improvement for models that are based on the differentiation of stem cells (hPSC or adult progenitors) into mature functional derivatives and, on the other hand, the standardization of formulations will come particularly handy when spatiotemporal delivery of tissue-specific and application-specific environmental cues are combined (i.e., homeostatic or pathophysiological conditions). Finally, monitoring and characterization of such models still relies on end-point, invasive assays; which delays validation of results, particularly for drug screening and toxicology studies. This calls for the development of in-line sensors that report both system parameters and cellular activity.

The aim of this Research Topic is to cover promising, recent, and novel research trends in 3D engineered organoids. Areas to be may include, but are not limited to, the following themes:

• Solutions to increase the diffusion and uptake of nutrients within 3D organoids and tissue constructs.
• Advances in the control of biophysical stimuli, including the generation of temporally controlled stiffness gradients.
• Advances in the design of organoids and engineered tissues to provide a functional model for adoption by pharmaceutical and biotechnology companies.
• Reproducibility of miniaturized engineered tissue constructs for high throughput drug screening assays.
• New technologies to provide quantitative analysis in living 3D cell culture systems, including spatio-temporal and longitudinal measurements.

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Keywords: 3D engineered organoids, Tissue Engineering, Assembloids, cell-cell interactions, cell-matrix interactions, Biochemical Engineering, Design of organids, miniaturized tissue, living 3D cell cultures

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