Compared with 3D culture using bulk hydrogel, the microgels with a permeable shell layer have a higher surface area for mass transfer which facilitates fast cell expansion. Encapsulating and co-culture of tumor cells with cancer-associated fibroblasts using this system forms miniaturized 3D tumor spheroids, which can be applied as in vitro disease models for anti-cancer drug screening. As the core matrix, gelatin provides biological recognition for cell adhesion, creating a beneficial microenvironment for cells. In particular, to culture different cell types (anchorage dependent cell and non-anchorage dependent cell), the concentration of GelMA and selective crosslinking can be controlled to achieve liquefied matrix, semi-liquid matrix or gel-matrix with different stiffness. The versatile and tunable platforms for core-shell based encapsulation offer defined structure and essential ECM for various 3D cell culture and co-culture in dynamic healthcare and disease applications.
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