Orthopedic implant-related bacterial infections and resultant
antibiotic-resistant
biofilms hinder implant–tissue integration and failure. Biofilm
quorum sensing (QS) communication determines the pathogen colonization
success. However, it remains unclear how implant modifications and
host cells are influenced by, or influence, QS. High aspect ratio
nanotopographies have shown to reduce biofilm formation of Pseudomonas aeruginosa, a sepsis causing pathogen with well-defined
QS molecules. Producing such nanotopographies in relevant orthopedic
materials (i.e., titanium) allows for probing QS using mass spectrometry-based
metabolomics. However, nanotopographies can reduce host cell adhesion
and regeneration. Therefore, we developed a polymer (poly(ethyl acrylate),
PEA) coating that organizes extracellular matrix proteins, promoting
bioactivity to host cells such as human mesenchymal stromal cells
(hMSCs), maintaining biofilm reduction. This allowed us to investigate
how hMSCs, after winning the race for the surface against pathogenic
cells, interact with the biofilm. Our approach revealed that nanotopographies
reduced major virulence pathways, such as LasR. The enhanced hMSCs
support provided by the coated nanotopographies was shown to suppress
virulence pathways and biofilm formation. Finally, we selected bioactive
metabolites and demonstrated that these could be used as adjuncts
to the nanostructured surfaces to reduce biofilm formation and enhance
hMSC activity. These surfaces make excellent models to study hMSC–pathogen
interactions and could be envisaged for use in novel orthopedic implants.