Microgel Matrices for Human Cancer Organoid Production

Abstract: Organoids are three-dimensional multicellular structures capable of mimicking tissue structure and tumour heterogeneity better than other available biological model systems. They are a powerful new enabling technology in drug discovery because they can give more accurate test results while enabling high throughput screening of drug candidates. However, traditional manual culture and expansion of organoids is labour intensive and expensive. In order for organoids to be widely used in industrial and clinical applications, their robust production must be scaled up efficiently. Cellesce Ldt has developed a process to grow large numbers of organoids for commercial drug screening but the methods rely heavily on very expensive animal-derived matrix scaffolds for organoid encapsulation, mainly Matrigel. These materials are both expensive to produce and are prone to batch-to-batch variations in the bioactive molecules which they contain. In this research, non-animal derived polymers were investigated to reduce Matrigel use as 3D organoid matrix, focusing on the production of cell-containing hydrogel microbeads. Material A and B, both hydrogel-forming biomaterials, were selected to form blends with Matrigel, thus providing a more sustainable and cost-effective means of organoid generation. The microbeads were produced by electrospraying and compared in terms of their physical properties. Finally, the ability of the cells to grow and form organoids within these blends was assessed and compared with the current method using Matrigel. This study concluded that the material A-based blends were the only ones that supported organoid growth, with the blend AM1 being the optimum blend among the others. The main outcome of this research will be the basis for future bioreactor and scale-up studies.

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