Silicon-based nanopillars: a novel platform for tissue applications

Nanostructured surfaces are increasingly used for cell applications due to their enhanced interactions with numerous cell types; yet, their effects on tissues remain unexplored. To address this limitation, we designed vertical silicon nanopillar (Si-NP) arrays with high density, high aspect ratio and submicrometer diameter, as an optimized geometry based on previous cell-nanostructure studies. Using state-of-the-art <i>in vitro</i> and <i>ex vivo</i> assays, we examined adhesion and biocompatibility of biological samples of different origin and level of complexity -human epithelial-like cell lines, <i>Drosophila</i> imaginal discs and patient-derived lung cancer biopsies-laid on Si-NP arrays or unpatterned flat Si surfaces. Our results demonstrated that Si-NP arrays significantly improved cell and tissue adhesion while preventing oxidative damage and early apoptosis. Consistently, focused ion beam-scanning electron microscopy imaging of cells and tissues showed extended horizontal protrusions and limited vertical wrapping around Si-NP, revealing enhanced cell-NP interactions without cell/tissue penetration. In contrast, flat Si surfaces showed poor adhesion, increased apoptosis, and failed to support tumor biopsy attachment. Interaction with Si-NP arrays upregulated reactive oxygen species (ROS), yet mitochondria-associated ROS remained unchanged, and consequently apoptosis was not induced, indicating that the increased ROS arose from non-mitochondrial compartments and did not compromise viability. Notably, Si-NP arrays matched or outperformed biological responses on tissue culture plastic and Transwell-based assays, which are common <i>in vitro</i> and <i>ex vivo</i> substrates, respectively. These findings provide the first demonstration of the biological suitability of Si-NP arrays for tissue applications in research and clinical translation.