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Abstract: Nanoclay-enabled self-supporting printing has been emerging as a promising filament-based extrusion fabrication approach for different biomedical and engineering applications including tissue engineering. With the addition of nanoclay powders, liquid build materials may exhibit solid-like behavior upon extrusion and can be directly printed in air into complex three-dimensional structures. The objective of this study is to investigate the effect of nanoclay on the extrudability of N-isopropylacrylamide (NIPAAm) and the effect of standoff distance on the print quality during nanoclay-enabled direct printing. It is found that the addition of nanoclay can significantly improve the NIPAAm extrudability and effectively eliminate die swelling in material extrusion. In addition, with the increase of standoff distance, deposited filaments change from over-deposited to well-defined to stretched to broken, the filament width decreases, and the print fidelity deteriorates. A mathematical model is further proposed to determine the optimal standoff distance to achieve better print fidelity during nanoclay-enabled direct printing. Based on the extrudability and standoff distance knowledge from this study, NIPAAm–Laponite nanoclay and NIPAAm–Laponite nanoclay–graphene oxide nanocomposite hydrogel precursors are successfully printed into a three-layered one-dimensional responsive pattern, demonstrating the good extrudability and print quality during nanoclay-enabled printing under optimal printing conditions.