## 4 Surface-Immobilized Peptides on Medical Implants  
Medical implant failure or malfunctioning are complex phenomena and can be attributed to many factors (Figure 1). To start with, the surface of medical implants can be colonized by bacteria during the implantation process, or at a later time point [14; 15], putting the performance and longevity of the implant at risk. Moreover, due to peri-implant tissue damage during the implantation procedure, the local immune responses at the implant-tissue interphase are dysregulated, thus rendering the peri-implant area more vulnerable to infections. These factors render the treatment of biomaterial-associated infection very complex. Traditional treatments, including prophylactic and systemic administration of antibiotics, or even combinations of them, often are unsuccessful in combating infections on medical implants, because of failing in establishing a sufficient antibiotic concentration at the implant site [20; 21; 22]. Hence, localized delivery of antimicrobial agents potentially eliminates issues such as systemic toxicity and excessive exposure to the antimicrobial agent, favouring the rising of resistant bacteria populations, and is therefore highly desirable [15; 23; 24; 25]. The development of resistance is a major problem for currently available antibiotic coatings, with one study indicating that gentamicin-resistant _Staphylococci_ were recovered from gentamicin-loaded beads implanted in a patient after arthroplasty [84], highlighting the dangers of the development of resistance from exposure to biomaterial-associated antimicrobials. Another important factor for the longevity of medical implants in vivo is the reduction of the  
Figure 1: Medical implant failure risk factors. inflammation at the peri-implant area (Figure 1) [85; 86], usually caused by bacterial components, such as lipopolysaccharideacharide (LPS), a component of the Gram-negative bacteria cell wall. LPS-induced macrophage recruitment at the implant site plays a key role in implant acceptance, as it initiates the inflammatory response, by pro-inflammatory cytokine release [85; 86]. However, few studies evaluate the potential of inflammatory reactions induced by implant coating [87]. On top of their antimicrobial activity, some AMPs also display anti-inflammatory properties by inhibiting the secretion of pro-inflammatory cytokines and chemokines, such as tumor necrosis factor (TNF)-\(\alpha\)[88] and upregulating the secretion of anti-inflammatory cytokines, such as IL-10 [89]. A promising antimicrobial strategy for the prevention of bacterial colonization on such surfaces and localised delivery of antimicrobial drugs at the peri-implant area, is coating the surface of the implant with antimicrobial compounds. There are two key questions one should raise when designing biomaterial with surface immobilized AMPs. For one, immobilization of peptide on a surface will potentially help to keep the surface sterile. But, for how long should the peptide be available on the surface? Should it be degraded or released? In order to achieve an ideal antimicrobial coating, for localized delivery of antimicrobial compound, it should display the following properties (Figure 2): (i) broad-spectrum antimicrobial activity; (ii) controlled kinetics of release and effective concentration when released, exceeding the MIC [90]; (iii) long term efficacy, resistance to degradation in vivo; (iv) biocompatibility; (v) stability under heat-sterilization; (vi) limited capacity to induce antimicrobial resistance. Moreover, depending on the use and the purpose, medical implants can be considered permanent e.g., orthopedic implants, artificial heart valves, or can be used on a temporary basis e.g., catheters, sutures, contact lenses. Due to this diversity, various types of materials are required for the manufacturing of medical implants, rendering the development of antimicrobial coatings more perplexing.