In vitro co-culture models for the assessment of orthopedic antibacterial biomaterials

Abstract

The antibacterial biofunctionality of bone implants is essential for the prevention and treatment of implant-associated infections (IAI). In vitro co-culture models are utilized to assess this and study bacteria-host cell interactions at the implant interface, aiding our understanding of biomaterial and the immune response against IAI without impeding the peri-implant bone tissue regeneration. This paper reviews existing co-culture models together with their characteristics, results, and clinical relevance. A total of 36 studies were found involving in vitro co-culture models between bacteria and osteogenic or immune cells at the interface with orthopedic antibacterial biomaterials. Most studies (∼67%) involved co-culture models of osteogenic cells and bacteria (osteo-bac), while 33% were co-culture models of immune cells and bacterial cells (im-bac). All models involve direct co-culture of two different cell types. The cell seeding sequence (simultaneous, bacteria-first, and cell-first) was used to mimic clinically relevant conditions and showed the greatest effect on the outcome for both types of co-culture models. The im-bac models are considered more relevant for early peri-implant infections, whereas the osteo-bac models suit late infections. The limitations of the current models and future directions to develop more relevant co-culture models to address specific research questions are also discussed.

Highly Cytocompatible Polylactic Acid Based Electrospun Microfibers Loaded with Silver Nanoparticles Generated onto Chestnut Shell Lignin for Targeted Antibacterial Activity and Antioxidant Action

“…In fact, the numbers of CFUs obtained by polystyrene (poly) and control mats (E, J, O) were comparable ( p > 0.05), thus demonstrating that, in the absence of a proper antibacterial agent, pathogens were able to adhere and colonize mats. SEM images provided a clear visual demonstration of such scenario as a high concentration of bacteria was observed in direct contact with cells that appeared as irreversibly damaged (indicated in the white boxes) by the metabolic activity of the bacteria producing toxins and proteolytic enzymes . On the contrary, cells reported a physiological morphology onto the Ag-doped mats, and the density of adhered viable bacteria was significantly reduced with particular regard to the I and N composites as shown by SEM images, thus confirming being the best ones in terms of antibacterial activity as previously reported in Figure .…”

“…SEM images provided a clear visual demonstration of such scenario as a high concentration of bacteria was observed in direct contact with cells that appeared as irreversibly damaged (indicated in the white boxes) by the metabolic activity of the bacteria producing toxins and proteolytic enzymes. 67 On the contrary, cells reported a physiological morphology onto the Ag-doped mats, and the density of adhered viable bacteria was significantly reduced with particular regard to the I and N composites as shown by SEM images, thus confirming being the best ones in terms of antibacterial activity as previously reported in Figure 6. In line with SEM imaging, the CFU number was significantly lower in comparison to the bulk control (p < 0.05, indicated by #, §, *), thus confirming that cell metabolism was favored over bacteria proliferation by the composition of the mats.…”