**2.2.1 Biofilms**

Biofilm-forming bacteria share the ability to colonize foreign implant materials by initial attachment to the surface, followed by agglomeration in multi-cellular layers. During the accumulation process the bacteria excrete matrix substances into which the infectious agents themselves become embedded. Due to alterations in cellular metabolism, regulated by complex signal pathways within the biofilm, the bacteria switch from the planktonic state to a sessile condition in which proliferation rates are extremely low (Costerton et al., 1999; Donlan & Costerton, 2002; Donlan, 2005; Gristina & Costerton, 1985).

Infections involving biofilm formation are both difficult to identify and to treat. On one hand, the biofilm matrix provides a substantial barrier to host defense mechanisms and to diffusion of antibiotics. On the other hand, the low proliferation levels of the sessile organisms may dramatically impair their antibiotic susceptibility, especially to bactericidal agents (Jones et al., 2001; Monzon et al., 2002; Stewart & Costerton, 2001), and their cultivation for diagnostic purposes in vitro.

As biofilm formation is a gradual process, this mechanism is the characteristic feature of late, low-grade infections. Implants with an established biofilm are definitely subject to removal although the causative agents are less virulent by themselves than the bacteria which cause early arthroplasty infections.

### **2.2.2 Periprosthetic membrane**

The periprosthetic membrane is the histomorphologic hallmark of joint implant failure. It is a seam of connective tissue which develops at the interface between the bone and the implant in the course of the inflammatory process that leads to septic or aseptic prosthetic loosening. Interestingly, there are four morphologic types which can be linked to different etiologies of inflammation. Of these, the infectious type (type II) is particularly often associated with periprosthetic infection. It is characterized by predominant infiltration with neutrophilic polymorphonuclear leukocytes (Krenn et al., 2011; Morawietz et al., 2006).

As the periprosthetic membrane must be removed if the surgical revision procedure is to be successful, it is ideal sample material for characterizing the type of inflammation by histology, thus providing valuable evidence for the underlying cause of implant loosening.

### **2.3 Inflammation parameters: Utility to detect infections**

Early periprosthetic infections are mostly associated with typical clinical signs of infectious disease. However, in low-grade (late) infections the clinical symptoms and radiologic signs are often unspecific and therefore not suitable for ruling out aseptic implant failure (Virolainen et al., 2002). Nuclear imaging techniques used to detect periprosthetic inflammation are generally regarded as optional tests which may be of use if the diagnosis cannot be established otherwise, but they are not recommended for routine application (Della Valle et al., 2010). In contrast, the following procedures do play important roles in patient assessment for arthroplasty infection.
