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Synthetic nanoclays are plate\u2010like polyions composed of simple or complex salts of silicic acids with a heterogeneous charge distribution and patchy interactions. Due to their biocompatible characteristics, unique shape, high surface\u2010to\u2010volume ratio, and charge, nanoclays are investigated for various biomedical applications. Here, a critical overview of the physical, chemical, and physiological interactions of nanoclay with biological moieties, including cells, proteins, and polymers, is provided. The state\u2010of\u2010the\u2010art biomedical applications of 2D nanoclay in regenerative medicine, therapeutic delivery, and additive manufacturing are reviewed. 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