Life and death at the biomaterial surface Host response and novel antimicrobial strategies against biomaterial-associated infection

The use of biomaterials has increased steadily in the last decades. Biomaterial-associated infection (BAI) is a complication of implantation of a biomaterial, and is predominantly caused by Staphylococcus aureus, Staphylococcus epidermidis, Candida albicans or Candidozyma auris. Pathogens can colonize the implant surface and form biofilms, allowing evasion of host immune responses and limiting effectivity of antimicrobial treatment. Additionally, rising antibiotic resistance further complicates treatment. This thesis aimed to develop and assess alternative non-antibiotic strategies to prevent BAI, and explore the host response to infection in the presence of a biomaterial. We developed a carboxylated graphene quantum dots thin film with potent bactericidal activity against drug-resistant S. aureus and E. coli, and potent fungicidal activity against C. albicans and drug-resistant C. auris when applied to catheters. To explore other non-antibiotic antimicrobial strategies, we developed a titanium implant coating based on polyethyleneimine and sodium iodide, and demonstrated promising in vivo antibacterial activity against S. aureus. Furthermore, we aimed to elucidate the molecular mechanisms of the host response to BAI associated with the high susceptibility to infection due to the presence of a biomaterial using gene expression analysis in a subcutaneous implant S. epidermidis infection mouse model. We concluded that early immune skewing to an interferon type I response in BAI resulted in persisting infection even at late time points. Overall, this thesis describes novel non-antibiotic antimicrobial strategies and their antimicrobial activity against various pathogens, and novel insights into the host response to BAI to further enhance development of prevention and treatment strategies.