Modulation of cardiovascular device infection by biomaterial surface chemistry and shear stress.

摘要

Infection of implanted cardiovascular biomaterials poses a serious complication and involves multifaceted interactions involving bacteria, the implant surface, the presence of host proteins, and local hydrodynamic conditions. These infections are initiated by bacterial adhesion to the surface of the implant followed by colonization and biofilm formation. Our hypothesis is that modification of biomaterial surface chemistry can diminish the probability of cardiovascular device infection by impeding initial bacterial adhesion and subsequent biofilm formation.; A rotating disc model, which generates shear stress within a physiological range, was used to characterize adhesion of leukocytes and Staphylococcus epidermidis on polyurethanes modified with surface modifying endgroups (SMEs) and phospholipid polymer surfaces under dynamic flow conditions. Leukocyte adhesion in serum exhibited a shear dependency with polyethylene oxide SMEs and phospholipid polymer surfaces strongly inhibiting leukocyte adhesion. Bacterial adhesion was primarily independent of material and shear stress effects in serum, and diminished significantly to ≤10% compared to serum-free media. This suggests that protein adsorption may play a greater role in limiting initial bacterial adhesion than surface chemistry effects. While initial S. epidermidis adhesion is inhibited in the presence of adsorbed proteins, interbacterial adhesion, possibly aided by slime production, leads to the formation of a robust mature biofilm. However, the formation of biofilm can be impeded by biomaterial surface chemistry. Modification of cardiovascular biomaterials with PEO endgroups significantly reduced S. epidermidis adhesion, colonization, and biofilm formation over 48 hours. Therefore, the effects of biomaterial surface chemistry are not present in the early stages of biofilm development but manifest themselves in the long term behavior of bacteria by modulating adhesion, accumulation, and slime production over time.; Biomaterial surface chemistry influences leukocyte adhesion and function resulting in a compromised host response. PEO has detrimental effects on adherent neutrophils as indicated by a decrease in production over time of O2 - and NO in response to a stimulus. Our results also suggest that bactericidal mechanisms in neutrophils involving NO generation (NOS pathway) are further compromised than O2 - producing pathways (NADPH oxidase) upon exposure to biomaterials resulting in a diminished microbial killing capacity which can increase the probability of device centered infections.