Leveraging the Concentration-Gradient Diffusion within a Catalyst-Containing Hydrogel Bilayer Enables Safe and Effective Tooth Whitening and Caries Prevention

Tooth whitening has attracted considerable attention as it can enhance appearance and improve oral health. Nanocatalysts with peroxidase-like activity can catalyze H 2 O 2 to generate reactive oxygen species (ROS), a process known as chemodynamic therapy (CDT). The ROS generation can achieve effective tooth whitening and caries prevention. Nonetheless, traditional CDT methods often struggle with controlling the reaction process by adjusting the concentrations of H 2 O 2 or nanocatalysts. An excessive ROS can harm oral tissues, whereas insufficient ROS may compromise therapeutic efficacy. To address this issue, this study designed a hydrogel bilayer that separately encapsulates H 2 O 2 and iron-based metal–organic frameworks (Fe-MOFs) nanoparticles (NPs) with peroxidase-like activity. The ROS generation was regulated by leveraging the concentration-gradient diffusion of H 2 O 2 . Through Monte Carlo simulations and machine learning algorithms, mathematical formulas were derived to elucidate how to harness concentration-gradient diffusion for near-independent modulation of the reaction half-life and rate. The experimental results demonstrated that being guided by the formulas could effectively avoid the initial burst of ROS and manipulate the ROS generation duration, thereby achieving safe and effective tooth whitening and caries prevention. We anticipate that this bilayer design strategy can be extended to other CDT systems, enabling precise control over therapeutic outcomes.