Dual Antibacterial and Soft-Tissue-Integrative Effect of Combined Strontium Acetate and Silver Nitrate on Peri-Implant Environment: Insights from Multispecies Biofilms and a 3D Coculture Model

Creation of a biological seal and efficient antibacterial qualities in the peri-implant environment is essential for the success of dental implants. Therefore, novel multifunctional strategies are being developed to address these issues, aiming at the simultaneous improvement of tissue integration and hindering pathological biofilm formation. In this study, we investigated the effect of tissue-promotive strontium acetate (SrAc), antibacterial silver nitrate (AgNO₃), and their combination on oral soft tissue cells and an oral multispecies biofilm not only in monoculture setups but also in a three-dimensional (3D) implant-tissue-oral bacterial-biofilm model (INTERbACT model) that takes the naturally occurring interactions into account. Application of SrAc led to improved fibroblast migration in the monoculture setting, without impairment of metabolic activity, even upon additional AgNO₃ administration. Notably, the combined treatment of SrAc and AgNO₃ resulted in a synergistic antibacterial effect during biofilm formation as well as on early matured biofilms. Most interestingly, the antibacterial effect of the combined treatment was even further enhanced within the coculture setup leading to increased bacterial death and decreased biofilm volume. The 3D tissue in the coculture setup underwent the combined treatment with a notable rise in CCL20 and IL-1β levels. Histologically, only the AgNO₃-treated groups exhibited damage to the integrity of the epithelial barrier. Therefore, the results of this study demonstrated promising dual antibacterial and tissue-integrative characteristics of combined AgNO₃ and SrAc in the dental implant environment. Additionally, the study emphasizes the importance of considering naturally occurring tissue-bacteria interactions for reliable <i>in vitro</i> testing of novel implant materials.