Orthopaedic implant infection is a devastating disease because of the physical and emotional trauma the patient encounters that is associated with revisional surgery, compounded by the long-term postoperative treatment needed.9,30 Current rates of infection for artificial joints (for the lifetime of an implant) vary by hospital, surgeon, and study, but the best estimates suggest an infection rate of 1 to 2%, which produces a figure of 4000 to 8000 infected arthroplasties requiring surgical revision annually. Implant infection is not limited to orthopaedic implants; it is conservatively estimated that there are 1.32 million prosthetic devices that become infected each year in the United States (Table 1). The cost is enormous, as is the morbidity and patient suffering caused by these persistent infections. Chronic infections are associated with bacterial biofilms which are characterized by microcolonies of bacteria encased in a protective extracellular polymeric matrix. Bacterial biofilms can form on any artificial surface that has been introduced into the human body, as well as on tissues adjacent to the implanted surface. It is important to emphasize that artificial joints of any type (hips, knees, elbows, etc); orthopaedic screws, bolts and rods are all vulnerable to hosting a biofilm.30 Implant infections can result acutely when infectious bacteria enter the implant site during surgery or recovery. However, many implant infections are subacute or chronic (20, 31) and result from systemic seeding of the implant following a septic event. Once a biofilm is established within the body, it is almost impossible to eradicate it, even with high doses of antibiotics.7,10 The biofilm also can produce periodic planktonic showers of bacteria (ie, bacteria shedding from the biofilm) into the bloodstream, which can result in episodic acute systemic infection in addition to the chronic infectious nidus for the patient.10 The biofilm model introduces a novel paradigm into microbiology and infectious disease, ie, the concept that bacteria have a life cycle just as many eukaryotes do.11 This knowledge provides us with a framework for understanding persistence and chronicity in bacterial infections, but more importantly it provides us with a starting place for the development of new approaches to the treatment of what have been intractable infections. Like all abiotic systems introduced into the human body, arthroplasties are prone to bacterial biofilm infections and even mixed-kingdom biofilm infections composed of bacterial and fungal species (Fig 1).
Biofilm bacteria, once firmly established on a nonliving surface within a host, essentially become a permanent feature of that surface7,9. There is no means, short of removing the infected device or killing the host, to eradicate the biofilm. Biofilms are not simply collections of individual bacteria, but rather are complex co-operative communities composed of one or more species of bacteria (and/or fungi) embedded within an extracellular matrix, displaying discrete temporal and spatial organizational properties and possessing a wide range of environmental sensing mechanisms linked to adaptive responses that operate at the population level rather than at the individual cell level (7, 9,13). This introduces an important concept with respect to biofilm pathogenesis in that the biofilm as a whole is acting as an organism instead of the bacterial cells acting individually (8,11). This realization provides for a fundamental change in our consideration of the evolutionary pressures that are operative on the bacteria. This duality of existence provides for an unprecedented level of adaptability and fitness for bacterial species that can transition between planktonic and biofilm environmental variants (envirovars). 9
From a medical perspective, the most important aspect of biofilm bacteria is their near imperviousness to elimination by either host defense mechanisms or even intensive long-term antimicrobial therapy. We have shown that these resistances to host and pharmacologic attack result in part from the fact that bacterial biofilms contain many different environmental niches with respect to nutrient availability and pH and O2 tension. The bacteria composing the biofilm express multiple phenotypes in response to these substrate gradients.4,24 Therefore, the bacteria possess a phenotypic plurality that ensures that some subpopulation of them will survive any type of antibiotic treatment based on metabolic considerations.7,9,10,26 Moreover, the bacteria within a biofilm function cooperatively, analogous to a simple metazoan. At this stage of their life cycle, natural selection pressures will occur at the population level, as opposed to the individual cell during planktonic growth. We posit that it is this duality of existence modes that provide bacteria with their extraordinary fitness.11 In the presence of abundant nutrient sources and the absence of severe environmental threats, bacteria will grow as rapid planktonic blooms, but in the face of adversity they will adapt and persist as biofilms.
In this paper we describe two engineering-based approaches for the detection and control of biofilm infections associated with orthopaedic implants that can be deployed in situ. The economics of the treatment of individual infected arthroplasties multiplied by the large numbers of people affected by implant infections justify the increased costs associated with the development and manufacture of such “intelligent implants.” Such devices would be engineered to have multifunctional capabilities including bacterial diagnostics, treatment regimens with automonitoring of dispensed pharmaceuticals, and telemetry to provide feedback regarding the microbiologic and pharmacologic state of the joint.