Impact of antibacterial therapeutic agents on biofilm-tissue interactions in a 3D implant-tissue-oral-bacterial-biofilm model

Bacterial biofilms on dental implants can lead to peri-implant infections and demonstrate a remarkable ability to evade host immunity and resist antibiotics. Advanced in vitro models, such as the three-dimensional implant-tissue-oral-bacterial-biofilm model (INTER(b)ACT), are essential to evaluate antibiofilm efficacy. The INTER(b)ACT model, effectively reproduces the complex triangular interactions between an organotypic oral mucosa, an integrated implant and an oral multispecies biofilms, in the peri-implant situation. Here, we investigated the effect of antibacterial agents (chlorhexidine, amoxicillin, ciprofloxacin, doxycycline, and metronidazole) on biofilm-tissue interactions in the INTER(b)ACT model. While the antibacterial interventions had no effect on biofilm volume, all agents decreased the proportion of viable bacteria, underscoring their effect on bacterial viability despite biofilm resilience. Biofilm exposure to untreated tissues caused epithelial damage, whereas all antibacterial agents preserved epithelial integrity. However, the modulation of pro-inflammatory response differed between the various agents. All antibacterial treatments reduced hBD-2 and TIMP-1 levels. While doxycycline decreased IL-1β and CCL20, chlorhexidine lowered TNF-α level. In conclusion, the INTER(b)ACT model allowed the successful assessment of antibacterial efficacy, elucidation of biofilm resistance and characterization of inflammation during peri-implant tissue-biofilm interactions. This validation highlights the model's potential as a platform for developing and evaluating new therapeutic strategies for peri-implant diseases.