Nanotopography Influences\nHost–Pathogen Quorum\nSensing and Facilitates Selection of Bioactive Metabolites in Mesenchymal\nStromal Cells and <i>Pseudomonas aeruginosa</i> Co-Cultures

Orthopedic implant-related bacterial infections and resultant\nantibiotic-resistant\nbiofilms hinder implant–tissue integration and failure. Biofilm\nquorum sensing (QS) communication determines the pathogen colonization\nsuccess. However, it remains unclear how implant modifications and\nhost cells are influenced by, or influence, QS. High aspect ratio\nnanotopographies have shown to reduce biofilm formation of <i>Pseudomonas aeruginosa</i>, a sepsis causing pathogen with well-defined\nQS molecules. Producing such nanotopographies in relevant orthopedic\nmaterials (i.e., titanium) allows for probing QS using mass spectrometry-based\nmetabolomics. However, nanotopographies can reduce host cell adhesion\nand regeneration. Therefore, we developed a polymer (poly(ethyl acrylate),\nPEA) coating that organizes extracellular matrix proteins, promoting\nbioactivity to host cells such as human mesenchymal stromal cells\n(hMSCs), maintaining biofilm reduction. This allowed us to investigate\nhow hMSCs, after winning the race for the surface against pathogenic\ncells, interact with the biofilm. Our approach revealed that nanotopographies\nreduced major virulence pathways, such as LasR. The enhanced hMSCs\nsupport provided by the coated nanotopographies was shown to suppress\nvirulence pathways and biofilm formation. Finally, we selected bioactive\nmetabolites and demonstrated that these could be used as adjuncts\nto the nanostructured surfaces to reduce biofilm formation and enhance\nhMSC activity. These surfaces make excellent models to study hMSC–pathogen\ninteractions and could be envisaged for use in novel orthopedic implants.