Beyond roughness: Lateral surface architecture drives Candida albicans virulence on denture polymers

Surface roughness is widely regarded as the primary determinant of microbial adhesion to dental biomaterials. However, this framework overlooks the potential role of lateral feature spacing. This study investigated whether lateral surface topographical architecture, quantified by spatial autocorrelation length (SAL), contributes to the regulation of Candida albicans virulence-associated biofilm traits on dental polymer surfaces.

Additively manufactured poly(methyl methacrylate) (PMMA) substrates were engineered to decouple vertical roughness amplitude from lateral surface spatial organization (LS). Nominally smooth (Ra ∼ 0.1 µm) and rough (Ra ∼ 1.8 µm) surfaces were fabricated with either narrow (frequent lateral feature spacing) or wide (broad lateral feature spacing) SAL. Surface topography was characterized using profilometry and autocorrelation analysis. C. albicans biofilms were cultured on the substrates and assessed for viability, biomass, extracellular polymeric substance (EPS) production, metabolic and proteolytic activities, and hyphal morphogenesis using quantitative assays and fluorescence microscopy.

Surface roughness primarily influenced biofilm retention and hyphal transformation, whereas LS emerged as a regulator of virulence-associated phenotypes. Narrow-LS surfaces significantly increased biofilm viability, EPS production, protease activity, and metabolic output compared with Wide-LS surfaces, independent of roughness amplitude. Notably, even nominally smooth surfaces (Ra < 0.2 µm) with narrow LS exhibited virulence levels comparable to those observed on rough, unpolished surfaces (Ra = 1.8 µm), highlighting the strong contribution of LS in driving fungal pathogenic activation.

These findings identify lateral surface architecture as a critical determinant of fungal virulence on PMMA and support the development of antifungal material designs and polishing strategies based on controlled lateral surface organization rather than roughness alone.