Dr. Muhammad Imran Rahim (Hannover, DE), Dr. Carina Mikolai (Hannover, DE), Shuli Chen (Hannover, DE), Henning Hartwig (Hannover, DE), Jennifer Ulrich (Hannover, DE), Diana Strauch (Hannover, DE), Dr. Andreas Winkel (Hannover, DE), Dr. Katharina Nikutta-Doll (Hannover, DE), Dr. Daniela Paasch (Hannover, DE), Prof. Dr. Nico Lachmann (Hannover, DE), Prof. Dr. Dagmar Wirth (Braunschweig, DE), Prof. Dr. Henning Menzel (Braunschweig, DE), Prof. Dr. Meike Stiesch (Hannover, DE)
Abstract text (incl. figure legends and references)
Introduction
The formation of complex and antibiotic-resistant biofilms on medical implants can result in implant failure. Dental implant-related infections have a prevalence of 20-25 % five years after implantation. A detailed understanding of host-implant-biofilm interactions cannot be gained directly in an animal model or human body. Alternatively, two-dimensional (2D) cell culture models are usually employed; however, they cannot reflect the complexity of the tissue. Thus, three-dimensional (3D) culture models, particularly complemented with host immune cells, provide physiologically more relevant and predictive conditions under in vitro situations.
Objectives
This study aimed to establish a 3D-implant-tissue-oral-biofilm-model to investigate host-implant-biofilm interactions and evaluate the novel antibacterial implants.
Methods
A 3D mucosa model was developed by culturing human monocyte-derived macrophages, gingival fibroblasts and keratinocytes on a cylindrical titanium surface inside a collagen matrix. Cells in the 3D model were cultivated under standard cell culture conditions for 22 days at an air-liquid interface. Then, the constructs were analysed using histology and fluorescence microscopy. Further, cells were reisolated, subjected to flow cytometry, and evaluated for their activation status.
Results
The histological analysis confirmed that macrophages, fibroblasts and keratinocytes had successfully adhered to the inserted implants and were viable throughout the experiment. Flow cytometry analysis and ELISA demonstrated expression of CD14 and IL-1β, confirming the activation of macrophages. The co-culture assay confirmed antibacterial potential when macrophages were present.
Conclusion
The present study has successfully established a full-thickness 3D model consisting of three human cell types. The 3D model could be a promising in vitro system to investigate host-implant-biofilm interactions and evaluate novel antibacterial coatings.