Drying-Triggered Random Aggregation of Nanopillar Hydrogels with Strong Shape Distortion of Trapped Bacterial Cells

The emergence of antimicrobial resistance (AMR) due to the frequent use of antibiotics has become a crucial issue worldwide, with the development of alternatives that can reduce the use of conventional antibiotics being a key factor in tackling AMR. The use of nanopillar structures to stretch or physically disrupt bacterial cell walls has attracted attention as an alternative to antibiotics. However, factors that enhance the antibacterial activity of nanopillar structures, such as the aspect ratio, width, surface properties, hardness, and drying process of nanopillars, remain poorly understood. Based on our serendipitous discovery that our developed nanopillar hydrogels (with small diameters and large aspect ratios) formed heterogeneous and more random aggregates triggered by water evaporation, we further explored their antibacterial activity. In this study, we demonstrated that the drying-triggered random aggregation of the nanopillar hydrogels strongly distorts the bacterial cell shapes and enhances the antibacterial activity against both Gram-negative and Gram-positive bacteria. The circularity of Staphylococcus aureus ( S. aureus ) cells trapped in the nanopillar hydrogels exhibiting more random aggregation was distorted by approximately 2.7 times more than in flat hydrogels; furthermore, the survival rate was reduced to 49–52%. In addition, the capture and distortion of the shape of methicillin-resistant S. aureus, an AMR, by the nanopillar hydrogels were similar. Our findings suggest that “randomness” is a factor affecting the antibacterial activity of the nanopillars. Furthermore, our study offers solutions to problems associated with nanomaterials, such as large-area production and decomposition, by recycling the alumina substrate used to prepare the nanopillars and decomposing the nanopillars in an oxidizing environment.