**4. Biocompatibility, biotribology and biomechanics**

TKA was originally conceived as a procedure for elderly patients with low to moderate activity levels. As the survival rates increased to more than 90% after 10 years due to advances in the bearing materials [35–37], this procedure was expanded to younger and more active patients. However, register data has shown a decrease in the survival rate during the second and third decades of clinical performance [38–40], particularly in younger patients [38].

The most common causes for revision surgery in TKA are aseptic loosening including wear-induced osteolysis and periprosthetic infection. Aseptic loosening is a direct consequence of wear particles (metallic and polyethylene) released by the articulating surfaces, which are phagocytized by macrophages and giant cells that induce the liberation of proinflammatory cytokines (interleukins IL-1ß, IL-6, and the TNF-α), which, in turn, stimulate the osteoclasts and reduce the activity of the osteoblasts. As a result, an osteolytic activity at the implant-bone interface occurs, resulting in a loosening of the implant components. This inflammatory response is dependent on the amount of wear particles, as well as their type, size and shape [16, 22, 41–45]. For this reason, younger and more active patients that generate more wear particles during a longer period of time, are at a higher risk of revision due to aseptic loosening and wear [46].

One important requirement for the coatings is that they should be able to generate the same amount of wear or less as their uncoated versions and the coating should be able to withstand the whole clinical lifespan of the implant. In order to evaluate and compare the wear behavior of different knee implants, the standardized wear test ISO 14243 is performed. During this test, the knee implants are subjected to a serumbased test medium at 37°C to the motion and loading profiles of the level walking activity of a 75 kg person for a total of 5 million cycles.

Another important aspect regarding the wear behavior of the coated implants is the analysis of the metal ion and particle release, as a relationship between cobalt and chromium blood levels and failure of implants has been demonstrated [47–50]. Retrieval and in vitro studies have shown that the CoCrMo femoral components develop scratches through their articulation with the ultra-high molecular weight polyethylene (UHMWPE) gliding surface and thus release metal ions [17, 51–55].

### **4.1 Biocompatibility**

Zirconium material and Titanium-based coatings are considered as very biocompatible surfaces [56]. Several cell-culture and animal laboratory studies have shown that TiN coatings do not increase cell activity, show no difference to Ti6Al4V and have lower adhesion and proliferation over 24 hours of bacteria cultures than other uncoated metals [3]. Furthermore, in biocompatibility tests, TiN-coated test specimens made out of cobalt-chromium and titanium alloys did not cause any biotoxic damage [57].

Regarding ZrN multilayer coating Thomas et al. [48] performed patch tests on patients with and without metal ion hypersensitivity and showed no allergic reaction to the ZrN multilayer coated probes. Moreover, implanted multilayer-coated sticks in rabbits showed no adverse reactions to bone or tissues. Finally, a laboratory test with bacterial contamination showed 45% less biofilm formation on the ZrN multilayer coated surface in comparison to CoCrMo [58].
