Manual Biomaterials Associated Infection: Immunological Aspects and Antimicrobial Strategies

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Other factors that have also been related to difficulties in the treatment of medical device-related infections are functional abnormalities in the activity of phagocytic cells in contact with the foreign body and the presence of intracellular bacteria. While the anatomical location of the medical device can determine certain aspects of the treatment of these infections, this therapy must include an appropriate and lengthy antibiotic treatment combined with adequate surgical intervention.

Antimicrobial therapy needs to be carefully designed, and the antibiotics to use against device-related infections can be chosen according both to their activity against bacterial biofilms and nongrowing microorganisms, and to their intracellular efficacy. The specific characteristics of medical device-related infections, as well as the difficulties involved in their treatment, mean that multidisciplinary medical teams are required to ensure the optimal approach to and management of this pathology. Transcutaneous medical devices are indispensible in medicine.

Infection is the most frequently reported complication of indwelling devices and is associated with substantial costs, morbidity, and even mortality. Since antibiotics have limited efficacy in the treatment of such infections, removal of the device is required to eradicate the infection in a considerable number of cases.

Therefore, measures to prevent contamination of devices during and after insertion are of crucial importance to minimize the incidence of device-related infection. Strategies to reduce the risk for contamination of transcutaneous devices with skin bacteria include 1 hygiene measures during surgery, 2 promoting integration of implanted devices with host tissues, 3 surface modification of the device to prevent adherence of bacteria, and 4 topical antimicrobial prophylaxis.

Use of antibiotics for topical antimicrobial prophylaxis is strongly discouraged in view of the risk for resistance development. Antiseptics can be effective to reduce the incidence of infection of transcutaneous devices, but application of these compounds is mainly restricted to superficial skin disinfection. Therefore, alternative antimicrobial strategies are urgently needed. The potential of antimicrobial peptides and of honey as novel antimicrobial agents to prevent infection of transcutaneous devices is discussed.

Contemporary Restorative and Regenerative Dentistry mandates the use of implantable devices, as part of the overall treatment plan. The ultimate aim is to restore missing teeth or regenerate defective tissues. This can be achieved by the implementation of devices such osseointegrated dental implants or tissue regeneration materials, respectively.

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The oral cavity is rich in microbiota, which have the capacity to form polymicrobial biofilm communities on natural or artificial surfaces. It is therefore inevitable that implanted dental devices are also prone to microbial colonisation, and associated oral infections, such as peri-implantitis. Treatment of these infections involves the elimination of the causative factor biofilms and restoration of the structure and function of the affected tissues.

The present chapter is discussing the aetiology, pathogenesis, diagnosis and therapeutic challenges of these newly emerged infections of the oral cavity. Musculoskeletal infection remains a great challenge in orthopedic and trauma surgery.

Despite best medical and surgical practice and significant advances in research and development, bone and implant associated infections are still difficult to diagnose, impossible to prevent in all cases and require invasive and debilitating treatment. The development and safe clinical implementation of novel preventative, therapeutic or diagnostic strategies requires the use of animal models of infection, which provide crucial evidence regarding performance, cytocompatibility, biocompatibility, and safety prior to clinical implementation.

Many animal models of musculoskeletal infection have been described in the literature; however, there remains a dearth of fully standardized or universally accepted reference models hindering advancement in the field. The following chapter provides an overview of the animal models available for the study of musculoskeletal infection, the latest advances that are expected to improve them, and some of the most important scientific output achieved using these models.


Staphylococcus epidermidis in biomaterial-associated infections

Geoff Richards, T. Fintan Moriarty. Biomaterials and medical device designs have become progressively more complex to accommodate diverse demands for performance and safety in vivo. While a majority of these implants satisfy their clinical expectations with safety and efficacy in their specific applications, a minority of implants induce serious adverse events with substantial health and economic consequences.

One recognized challenge is the growing clinical problem with implant-associated infections. Increasing number and types of implants used in patients have resulted in increasing numbers of biomaterial-associated infections. Researchers and medical device manufacturers have responded to this challenge with intensified attention to innovating device designs, surgical implantation protocols, and biomaterials to minimize infection opportunities. Medical devices with claims to limit microbial adhesion and colonization using combinations of pharmacological, topological, and materials chemistry approaches have been brought into clinical use with the intent of reducing device-related infections.

Many types of catheters, stents, orthopedic devices, contact lenses, surgical meshes, shunts, sutures, cardiovascular replacements, and many other device categories offer antimicrobial enhancements. Approaches include different biomaterials chemistries that intrinsically resist microbial colonization or that deter active growth on contact, surface modifications that produce topologies observed to limit pathogen attachment, medicinal, antiseptic or bioactive coatings, direct antimicrobial attachment to surfaces, or drug impregnation within the biomaterial, and extended release strategies that control antimicrobial agent release from the device over time after implantation.

Despite considerable research and development efforts, the problem of infections related to biomedical devices and implants persists. Silver has attracted considerable interest for its ability to mitigate bacterial colonization of biomaterials surfaces in vitro and has been used in some commercial products such as wound bandages. Silver ion releasing biomaterials are thus considered to be promising candidates for rendering surfaces of biomedical devices and implants resistant to bacterial attachment.

Here we review a number of strategies used for the design of antibacterial coatings containing silver. We also discuss the continuing controversy regarding the potential for silver ions to exert adverse effects on human cells and tissue. Finally we briefly compare the silver release approach with the alternative strategy of antibacterial coatings comprising organic antibiotics covalently coupled onto biomaterials surfaces.


The main cause of failure of biomedical implants is bacterial infections. Despite all efforts, it will never be possible to completely free operating theaters from bacteria, as human bodies contain already 10 14 bacteria.

Once on a surface, bacteria start proliferating, while protecting themselves with a slime layer against the immune system and administered antibiotics. A promising route to prevent or at least reduce bacterial infections caused by implants is by making surfaces of the devices antibacterial. One way to eradicate bacteria on implants is by contact killing. Quaternary ammonium compounds quats are very potent biocides. The generally accepted mechanism is that quats destabilize the cytoplasmic membrane, which leads to leakage and eventually to cell death. Unfortunately, a similar mechanism provokes cytotoxicity.

Fortunately, it is feasible to optimize the balance between biocidal activity and cytotoxicity by adapting the chemical structures. Low molecular weight quats are effective, but leachable and thus only temporarily effective. Moreover, leachable quats will be transported throughout the whole body and may cause cell lysis.

A more sustainable approach is to immobilize quats on surfaces. Although this development is still in an early stage in the last decade much progress has been made. There is a vast amount of literature describing successful in vitro experiments, and a number of papers have shown antibacterial activity in vivo.

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One promising strategy to combat this problem is the functionalization of the device surface with a dense layer of polymer chains which can resist bacterial adhesion and colonization. This article focuses mainly on polymer coatings which achieved the antibacterial effect without the leaching of the bactericidal components into the environment. Musculoskeletal infection is one of the most common complications associated with surgical fixation of bones fractured during trauma.

Severe fractures with extensive tissue damage are particularly prone to infection due to the high risk of wound contamination and compromised vascularity in the affected tissues. An infection associated with a fracture fixation device can delay healing, greatly increase patient morbidity, require multiple surgeries for effective treatment outcomes, and may tremendously increase treatment costs.

In the following chapter, two approaches to reduce the incidence of infection associated with fracture fixation devices will be described. The first is a passive approach involving aspects of implant design and application, whereby the implant used and the techniques used to place them can influence resistance to infection, at least in animal studies.

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The second approach involves antibiotic-coated intramedullary nails with a focus on two different gentamicin coatings. Gerhard Schmidmaier, Abhay D. Gahukamble, T. Fintan Moriarty, R. Geoff Richards. The Foley indwelling bladder catheter is the most commonly deployed prosthetic medical device.

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While this catheter provides a convenient way to drain urine from the bladder, it also provides easy access to the bladder for bacteria contaminating the skin insertion site. In addition the catheter undermines the basic antibacterial defenses within the lower urinary tract. As a result, catheter-associated urinary tract infections are the most common infections acquired by patients in healthcare facilities. Bacterial biofilms form readily on these catheters and play important roles in the pathogenesis of the conditions that complicate the care and seriously threaten the health of catheterized patients.

This chapter reviews the many attempts that have been made to prevent infection and biofilm formation by incorporating antimicrobial agents such as silver, nitrofurazone, minocycline, rifampicin, other antibiotics and biocides into catheters.

The failure of antimicrobial catheters to prevent the development of the particularly troublesome crystalline biofilms is discussed and the need explained for fundamental changes in the design of catheters. Vascular catheters constitute an essential component of modern health care. The escalating use of vascular catheters has highlighted the need to optimize prevention of infectious complications. Bloodstream infection is the most common serious complication of indwelling vascular catheters.

Although strict implementation of traditional infection control measures continues to be the primary measure for preventing infection, the level of adherence by medical staff to such measures varies over time, between different units, and across various medical centers. This limitation underscores the need to assess the potential clinical impact of surface modification of vascular catheters.

Since catheter colonization can be a prelude to infection, antimicrobial modification of the surfaces of catheters has the potential of not only inhibiting bacterial colonization of the catheter surfaces but also reducing the incidence of catheter-related bloodstream infection. A number of antimicrobial-modified vascular catheters are currently available for patient care, but they differ with regard to the type of antimicrobials, application on the external versus internal catheter surfaces, spectrum and durability of antimicrobial activity, and the ability to clinically protect against catheter-related bloodstream infection.

Scientific evidence should guide the present and future applications of antimicrobial-modified catheters. Implant mucositis and peri-implantitis have an infectious etiology. If left untreated the inflammatory responses and the infection will result in loss of alveolar bone around dental implants. Clinically, this is combined with edema and redness of the soft tissues surrounding the implant. The ultimate consequences of implant mucositis and peri-implantitis may be loss of the implant.

Dental implant manufacturers have focused on implant design, ease of placement, esthetics, and new prosthetic components.