Molecular and cellular interactions on noble metal nanopatterned surfaces − applications towards bone, soft tissue and infection control

Sammanfattning: Biomaterial-associated infection is recognised as one of the main risks for failure of medical devices. The presence of a foreign material in tissues has been suggested to compromise the ability of host cells to eradicate infection. In addition, a protective biofilm formed by bacteria limits the effectiveness of administered antibiotics, which underscores the importance of preventive measures. The use of implant surface modifications that resist bacteria is a promising approach to reduce the infection risk. A nanopatterned noble metal coating, applied on catheters, has shown up to 50% reduction of infections in the clinic. The aim of the present project was to investigate the material−tissue interactions of nanopatterned noble metal coatings, especially with respect to their role in inflammation and bioburden control. Several microscopy techniques, cellular and microbiological techniques, and molecular analyses have been used. The results show that the processes of inflammation and fibrosis can be modulated depending on the combination of noble metals in the coating (silver, gold and palladium). Noble metal coated titanium implants displayed a comparable bone response to that of clinically used machined titanium and was shown to reduce Staphylococcus aureus adhesion in vitro. To separate the effects of noble metal chemistry from nanotexture, the specific effects of nanostructures on host defence cells (monocytes) and Staphylococcus epidermidis were evaluated using gold model surfaces with or without immobilised gold nanoparticles on the surface. The presence of nanostructures did not affect monocyte behaviour but reduced bacterial viability and biofilm formation on the surfaces, indicating a bactericidal effect induced by nanoscale surface features. An in vivo infection model to study early inflammatory events was developed. The presence of S. epidermidis induced significantly more inflammatory cell recruitment, cell activity and cell death. A trend towards a more intense inflammatory response and a reduced amount of viable bacteria was observed around the noble metal coated implants. In conclusion, nanostructured noble metal coatings are biocompatible in soft tissue and bone, which render them a suitable option in many new application areas. The anti-infectious potential of the coatings may partly be related to physical interactions of bacteria with the surface nanostructures and partly related to an intensified inflammatory response due to the material surface chemistry.