Mikolai Carina, Wöll Kathrin, Rahim Muhammad Imran, Winkel Andreas, Falk Christine S, Stiesch Meike
Department of Prosthetic Dentistry and Biomedical Materials Science, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
Lower Saxony Centre for Biomedical Engineering, Implant Research and Development (NIFE), Stadtfelddamm 34, 30625, Hannover, Germany.
Sci Rep. 2025 May 30;15(1):18979. doi: 10.1038/s41598-025-03855-2.
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 (INTERACT), are essential to evaluate antibiofilm efficacy. The INTERACT 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 INTERACT 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 INTERACT 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.
牙种植体上的细菌生物膜可导致种植体周围感染，并表现出显著的逃避宿主免疫和抵抗抗生素的能力。先进的体外模型，如三维种植体-组织-口腔-细菌-生物膜模型（INTERACT），对于评估抗生物膜功效至关重要。INTERACT模型有效地再现了种植体周围情况下器官型口腔黏膜、一体化种植体和口腔多物种生物膜之间复杂的三角相互作用。在此，我们研究了抗菌剂（洗必泰、阿莫西林、环丙沙星、强力霉素和甲硝唑）对INTERACT模型中生物膜-组织相互作用的影响。虽然抗菌干预对生物膜体积没有影响，但所有药物都降低了活菌比例，这突出了它们尽管生物膜具有弹性但对细菌活力的影响。生物膜暴露于未处理的组织会导致上皮损伤，而所有抗菌剂都能保持上皮完整性。然而，各种药物对促炎反应的调节有所不同。所有抗菌治疗均降低了hBD-2和TIMP-1水平。虽然强力霉素降低了IL-1β和CCL20水平，但洗必泰降低了TNF-α水平。总之，INTERACT模型能够成功评估抗菌功效，阐明生物膜抗性，并表征种植体周围组织-生物膜相互作用期间的炎症。这种验证突出了该模型作为开发和评估种植体周围疾病新治疗策略平台的潜力。
