We have organized a multidisciplinary biomedical-engineering approach to develop a self-diagnosing, self-treating, self-monitoring artificial joint (Fig 2
; an “intelligent implant”) to combat the devastating problem of postimplantation bacterial biofilm infections that form on artificial joint prostheses. A meeting about such implant (Designing Intelligent Orthopaedic Implants for Biofilm Control) was held on April 10 to 12, 2003 in Big Sky, MT, which was attended by surgeons, microbiologists, biochemists, mechanical engineers, electrical engineers, and microelectromechanical systems (MEMS) engineers.
The most salient point made by the surgeons (with regard to implant design) was that a majority (> 60%) of arthroplasty infections result from two related staphylococcal species, Staphylococcus aureus and S. epidermidis. The microbiologists were united in their view that the infection should ideally be controlled before the formation of a biofilm because treatment regimens currently do not exist that can eradicate a biofilm on an abiotic surface implanted into human tissue. From the biosensor/MEMS engineers it was learned that the most difficult technical challenge is to overcome biofouling of an implanted device that would contain a membrane through which ligands would pass to induce a signal cascade. The electrical engineers indicated that the most problematic area for them was the need to provide power to the device for years without external leads which could become a source of infection. These consensus viewpoints, together with a preferred embodiment of what would be required in the design of an intelligent implant, were subsequently published 9
The overall concept in the design of an intelligent implant is to produce an arthroplasty that contains a MEMS-type biosensing device that can “eavesdrop” on bacterial communication systems associated with autoinduction, quorum sensing, and biofilm formation. Most pathogenic bacterial species (and most nonpathogenic species) respond to and produce intercellular signaling molecules that are designed to detect either the concentration of bacteria in a given locale (quorum sensing)23 or to determine the rate of diffusion within the ecosystem in which the bacteria find themselves.25 Depending on the bacterial species and the environment, quorum sensing serves to provide coordination of metabolic switching among a population of like bacteria so that they act in concert for the benefit of the population instead of as individual organisms. In the case of many pathogens, the detection of a quorum of bacteria induces the production of virulence factors and toxins. This co-ordinate-inducible phenomenon occurring on a population level has been interpreted as a survival strategy for pathogens wherein they try to remain “below the radar” of the host’s pathogen detection systems until such time because their numbers are great enough to overwhelm the host’s initial response. A classic example is S. aureus-induced toxic shock syndrome.19
On intercepting the bacterial signals, the MEMS biosensor will send a signal to a pair of integral gated reservoirs that will: 1) release inhibitory compounds that will prevent biofilm formation; and 2) release antibiotics at very high concentrations locally that will eradicate all planktonic bacteria that are in proximity to the joint before they establish a biofilm. The ability to provide site-specific dosing with antibiotics would have the benefit of being able to deliver much higher concentrations of antibiotics at the locus of infection than could be tolerated by the host through systemic treatment regimens. Moreover, local dosing would potentially permit the use of highly efficacious antimicrobials that have specific organ system toxicity profiles that makes them unusable with current systemic dosing regimens. Therefore, not only could this strategy provide for higher dosing levels of systemically tolerated antibiotics, but it could also increase the size of the available pharmacopoeia—a considerable advantage considering the high percentage of pathogenic strains that have acquired one or more planktonically active antibiotic resistance genes.
The MEMS biosensors and the drug reservoirs would be connected to a telemetry system embedded within the prostheses that would be accessible to the patient and physician using a handheld Bluetooth monitoring device, which in turn would be able to communicate with the wireless web. Therefore, patients would be able to take a reading anywhere in the world and upload the data to the internet, from which their physician could monitor the condition of the joint, regardless of location.