Engineered Brain Organoids on a 3D Scaffold Reveal Synaptic-Related Toxicity of Benzophenone-3 Associated with Wnt/β-catenin Dysregulation

Benzophenone-3 (BP-3), a common ultraviolet (UV) filter widely used in sunscreens, has raised increasing concern because early-life exposure may interfere with normal neurodevelopment. In this study, we fabricated a 3D inverse-opal polyethylene glycol diacrylate (PEGDA) scaffold and established a scaffold-supported brain organoid model for in vitro evaluation of BP-3-induced neurotoxicity. The scaffold was characterized by scanning electron microscopy (SEM), which revealed a highly ordered porous morphology with uniform pore size. It also showed good biocompatibility for organoid culture. BP-3 exposure induced concentration- and time-dependent toxicity in brain organoids, with more pronounced effects observed at 50 and 100 μM after 72 h of exposure. Under these defined exposure conditions, BP-3 was associated with increased oxidative stress, calcium-related functional changes, impaired membrane integrity, increased cytotoxicity, reduced expression of synaptic structural markers, and altered Wnt/β-catenin-related protein expression. These findings suggest that BP-3 exposure may disrupt early neurodevelopment-related processes in this model and is associated with synaptic-related alterations and Wnt/β-catenin dysregulation. Overall, this study supports the applicability of scaffold-supported brain organoids as an in vitro platform for evaluating BP-3-induced neurotoxic responses under controlled experimental conditions.