Composition Tuning\nof Semi-Open Cell Carriers via\nPhase Freeze-Shrink Self-Molding

Extracellular matrix (ECM)-mimicking microsized cell\ncarriers featuring\na semi-isolated chamber facilitate the study of cellular heterogeneity\nas well as intercellular communication. However, the semiopen shaping\nof the designated gel mixture remains unattainable with current methods.\nWe report an oil-phase freeze-shrink self-molding mechanism for generating\nsize- and composition-tunable cradle-shaped microgels (microcradles)\nfrom water-in-oil droplets. The universality of this shape transition\nprinciple is demonstrated with six types of polysaccharides dispersed\nin a poly(ethylene glycol) diacrylate (PEGDA) or methacrylate gelatin\n(GelMA) matrix. By doping the microcradles with the major ECM component,\nhyaluronic acid sodium, we demonstrate a label-free selective culture\nof CD44 receptor-rich cells and the formation of cell spheroids within\n3 days. This cryo-induced cradle-shaping strategy enables the functionalization\nof microcarriers for selective cell culture, thereby allowing them\nto be used for intercellular communication, drug delivery, and the\nconstruction of structural units for osteogenesis and 3D printing.