## 6 Biocompatibility and Implant Associated Infections  
The reliability of implantable electronics has undergone significant improvement over the last 50 years, mostly due to the advances in encapsulation and packaging designed to protect the indwelling module against the factors of the hostile environment [53]. Nonetheless, the issues with biocompatibility and the propensity of the implanted constructs to get infected over time remain. The highly invasive nature of many surgical procedures coupled with numerous serious health conditions and inadequate immune response frequently observed in the implant recipients make these individuals highly vulnerable to implant-associated infections [135]. Depending on the degree of severity, the complications may range from those that are painful and requiring localized antibiotic therapy to those which necessitate complete removal of the infected device and systemic antimicrobial therapy [63]. If left untreated, septicemia may develop, with potentially lethal consequences. The incidence of infections associated with cardiac pacemaker implant ranges from 1%-19%, with 7%-8% attributed to contamination during laboratory handling or the event of implantation [63]. Typically, biomaterial-associated infections can develop along several pathways, with peri- and post-operative contaminations being the most common route of introduction of the etiological agents [136, 137]. Patient-specific factors including diabetes mellitus and long-term anti-inflammatory medication of the patient using corticosteroids and other immunosuppressive drugs may slow down surgical site healing and patient recovery, making the host more susceptible to developing an infection [138]. In addition, the pathogens can originate elsewhere in the body, spreading to the implant site via blood to initiate late hematogenous infection. These can include implanted central venous catheter used for hemodialysis or other long-term access, a distant focus of primary infection, e.g., pneumonia, skin and soft tissue infections, and invasive procedures unrelated to the implanted device [139, 140]. This route of infection is particularly relevant to the implants that are exposed to the blood stream [141, 142]. The relatively high rate of implant-associated infections can be partially attributed to the fact that many of the physico-chemical attributed of the implanted surfaces render them a highly suited colonization ground for the bacteria. The non-living nature of the implant surface means that it does not respond to being colonized nor does it produce chemical signals to notify the surrounding tissues of the imminent danger. Certain combinations of surface properties can be employed to mitigate the initial stages of bacterial attachment; however they are powerless against bacterial cells that manage to adhere to the implant surface. Furthermore, bacterial cells have been demonstrated to release a vast array of extracellular polymeric substances to pre-condition a surface otherwise not suited for habitation or to form a three-dimensional polymer networks called biofilms. In their biofilm state, bacterial cells are protected against predation by the host immune cells and the effect of systemic drugs. Surfaces capable of both preventing the bacterial adhesion and replication, and eliminating attached bacteria by releasing antibacterial drugs are receiving significant attention. The drug eluting property can be imparted onto the implanted module via encapsulation or surface modification. In addition to traditional antibiotics, a range of alternative antimicrobial agents have been considered, including silver ions, nitric oxide, bioactive antibodies, and other bactericidal compounds [143, 144]. In a study by [PERSON] _et al._, the most common symptoms of infected antiarrhythmic devices were pocket erythema and local pain, with 68% of the pathogens being coagulase-negative staphylococci, followed by _Staphylococcus aureus_ (23%), and 13% multipathogen infections [145, 146, 147].