Translational organoid technology – the convergence of chemical, mechanical, and computational biology

The physical and mechanical features of extracellular materials and the spatiotemporal patterns of exogenous stimulation regulate cell behaviors and play pivotal roles in organoid development. Chemically defined media and scaffolding materials improve organoid reproducibility, but conditioned media and nature-derived materials hold promise in facilitating wider applications of organoids. Advances in engineering are increasingly being applied to organoid technology and to understanding the chemical, physical, and mechanical rules that govern cell signaling and organoid development. In many cases organoids are being evaluated by non-deep-learning algorithms because of limitations in the size and variance of training data and the challenge of data labeling. Successful clinical translation of organoid technology requires insights that extend beyond biology and biochemistry, notably from the fields of mechanical and computational biology. This review highlights recent advances in the organoid field that could potentially accelerate translation. We first review organoid fabrication methods, focusing on engineering approaches that increase organoid reproducibility, controllability, and production ability, as well as the physical conditions, culture media, and extracellular materials that regulate cell signaling and mechanotransduction. We then review computation-based organoid evaluation, including both information acquisition and data mining. Finally, we summarize the limitations of current advances and application horizons as well as the perspective of digital organoids. Successful clinical translation of organoid technology requires insights that extend beyond biology and biochemistry, notably from the fields of mechanical and computational biology. This review highlights recent advances in the organoid field that could potentially accelerate translation. We first review organoid fabrication methods, focusing on engineering approaches that increase organoid reproducibility, controllability, and production ability, as well as the physical conditions, culture media, and extracellular materials that regulate cell signaling and mechanotransduction. We then review computation-based organoid evaluation, including both information acquisition and data mining. Finally, we summarize the limitations of current advances and application horizons as well as the perspective of digital organoids. a short motif that mediates integrin interactions with its ligand proteins. It plays a key role in tumor angiogenesis, metastasis, and growth. formulations that mimic the ECM for cell culture purposes. a customized droplet-based microfluidics system for ultra-soft microgel fabrication and manipulation under surfactant-free conditions. The system is composed of multiple pieces of plastic tubing of identical lumen size that are sequentially connected with zero dead volume. stem cells derived from the undifferentiated inner mass cells of blastocysts. They are capable of self-renewal and can differentiate into all cell types of the body. the non-cellular component present within all tissues and organs which provides not only essential physical scaffolding for the cellular constituents but also initiates the crucial biochemical and biomechanical cues that are required for tissue morphogenesis, differentiation, and homeostasis. a photopolymerizable hydrogel composed of chemically treated collagen for use in tissue engineering applications. stem cells obtained by reprogramming of adult somatic cells, which regain the capacity for unlimited self-renewal and differentiation into multiple cell types. a family of highly homologous Zn2+-dependent endopeptidases that collectively cleave most if not all of ECM constituents. the approach of exposing pluripotent stem cells to signaling gradients that mimic developmental patterning. self-organized 3D organoids that are derived from isolated tissues of patient-derived xenografts. a nontoxic water-soluble fusogen that is commonly used in biological products. a technique in which RNA reverse transcription is followed by PCR amplification of the cDNA. the ratio of the intensity of a signal (meaningful information) to the intensity of background noise (self-generated signal during processing).