Immune cell surveillance and death on silicone catheter surfaces drives bacterial biofilm formation /

Includes bibliographical references

PhD;2024;Bioengineering

Silicone venous catheters are among the most used medical devices in the world with a prevalence of up to 80% in hospitalised patients. While they are used for several life-saving applications, they are also prone to nosocomial infections. In fact, 36% of all blood stream infections have been attributed to catheter use. Catheter infection causes encrustation and possible biofilm formation on the surface, requiring replacement of the catheter and treatment of the associated infection. Silicone is not inherently prone to bacterial adhesion; therefore, it is unclear as to what drives catheter infection and consequent biofilm formation. Previously, it has been shown that circulating innate immune cells such as neutrophils and monocytes, may adhere onto and die by apoptosis on silicone surfaces. Hence, we hypothesized that innate immune cell death on silicone catheter surfaces makes it conducive for bacteria to attach and form biofilms. Using an in vitro model system we developed in the lab, we show that prior immune cell surveillance of and death by apoptosis on the silicone surface leads to greater biofilm formation by various opportunistic bacteria that cause nosocomial infections. Further, we show that dead cell components on the surface are partly responsible for this. In a subsequent study, we show that once a biofilm has formed on a silicone surface coated with dead immune cell debris, neither neutrophils nor monocytes are able to clear the biofilm. These studies suggested that it was necessary to prevent immune cell adhesion and death on silicone surfaces, in addition to preventing bacterial attachment, to prevent catheter infection and biofilm formation. Thus, we coated silicone catheter surfaces with multi-electrolyte layers of polyarginine and hyaluronic acid and show that it prevents both immune cell attachment and consequent biofilm formation. Subsequently, we conclude that in order to prevent catheter infection and biofilm formation on catheter surfaces, it is imperative to minimize immune cell attachment and death as well as bacterial attachment on these surfaces.