TABLE 7.

Advantages and disadvantages of model setups.

3D Model setup	1st author	Advantages	Disadvantages
Organotypic dental implant model: fibroblasts containing scaffold with keratinocytes growing on top and integrated titanium in Airlift medium. Biofilm placed on top of the titanium implant	Ingendoh-Tsakmakidis, Mikolai	Keratinocytes form a multilayerds epithelium Interaction of fibroblasts and keratinocytes toward implant material possible Bacterial invasion along the implant close to clinical situation Biofilms show higher virulence then planktonic bacteria Multispecies biofilms also take interactions between different bacterial species into account (Mikolai et al., 2020)	Lack of bone tissue, immune cells and microfluidic dynamics Highly time consuming model setup Biofilm composition simplified compared to clinical situation Multispecies biofilm (Mikolai et al., 2020) reflects healthy state → pathogen biofilm missing
Transwell system with fibroblasts growing on implant material underneath a membrane filter and keratinocytes growing on top of the membrane	Ren	Cross-talk between cells without direct contact in presence of implant material can be studied High throughput and easy adaption to different implant materials possible Planktonic bacteria usage enables to change and mix bacterial species easily	No connection between keratinocytes and implant material → bacterial invasion not modeled realistically →impact of material properties on loosening of keratinocyte-implant interaction in case of inflammation cannot be studied Keratinocytes do not form multilayered epithelium Lack of bone cells, immune cells, microfluidic dynamic Planktonic bacteria are not reflecting clinical infection pathway of dental implants Higher virulence of biofilm compared to planktonic bacteria is not taken into account
Tissue engineered scaffold (developed to be implant material) seeded with cells and infected with bacteria containing medium	Bonifacio, Jia, Mohiti-Asli	Influence of material on cells and bacteria in Co-Culture can be evaluated High throughput during implant material development possible	No organotypic model to investigate infection routes ant interactions of cells, bacteria and materials Only 1 cell type used Lacking 3D tissue (e.g., bone tissue) into which the implant is incorporated Biofilm formation and higher virulence of biofilms not taken into account Implant materials not replaceable
Cell crown setup with THP-1 derived macrophages growing underneath a SIS-muc Scaffold with incorporated fibroblasts. Implant material is infected with biofilm and placed on top of SIS-muc	Murkar	Model includes immune cells Not specific for only one implant → outcomes applicable to different tissues Biofilm application takes higher virulence compared to planktonic bacteria into account Mixed-species biofilm takes interaction between bacterial species into account	No specified tissue addressed → further refinement for special tissues needed Makrophage reaction to scaffold material is not evaluated SIS-muc application limits height of the 3D model Model setup limits the application of implant materials with high weight