The silver solution to infection in knee implants

As demand for total knee replacements grows, Harry Hothi and the Smart Spacer Project team discuss the use of silver coatings on knee implants to reduce the risk of infection

The high demand of Total Knee Replacements (TKRs)

The demand for primary total knee replacements (TKRs) is now greater than that of total hip replacements (THRs).

In the UK alone, there have been over 871,472 primary TKRs performed since 2003, compared with 796,636 primary THRs [1]. As the patient population becomes larger, with greater expectations of mobility from younger, active patients, more of these patients are likely to outlive their implant, requiring at least one revision operation. Analysis of joint registry data for England and Wales by Patel et al. [2] predicted that the volume of primary TKRs will increase by 117 per cent between 2012 and 2030, while revision TKRs (Figure 1) will increase by 332 per cent in the same time-period.

The demand for primary TKRs in the US has been predicted to increase by 673 per cent by 2030 and the number of revision procedures could increase by 601 per cent by the same time [3], see Figure 2.

 

The infection problem

The reasons for early revision of an implant are multifactorial and often due to a combination of surgical, implant and patient factors. The National Joint Registry for England, Wales, Northern Ireland and the Isle of Man (NJR) reports that infection is one of the most common reasons for revision, accounting for 17 per cent of all cases [1]. This percentage may be an underestimate of the true figure as it is sometimes difficult to diagnose an infection that can be a key underlying factor in loosening, instability and pain. Furthermore, there is growing concern about the efficacy of traditional antibiotics due to an increase of antimicrobial resistance.

Figure 3 shows the additional burden in terms of length of stay and cost when comparing primary, septic and aseptic revision procedures with TKRs.

Current reference-standard for treatment

A two-stage revision operation is currently the most successful method for treating infection in patients with knee implants; 83 per cent of infections are treated this way [1]. A two-stage replacement first involves removal of the primary implant while retaining as much bone stock as possible and performing a thorough debridement. A temporary ‘spacer device’ is then implanted and is typically composed of an antibiotic cement to treat the infection together with intravenous antibiotics. After approximately six weeks the spacer is removed and a permanent implant replaced. Block spacers specifically designed for two-stage infections are an option used by some surgeons, see Figure 4. These can be loaded with a range of different antibiotics, such as Gentamicin, at various doses to help treat the infection but are not designed to offer stability or mobility to the patient. This often leads to soft-tissue contractures and issues with alignment over the treatment period.

There are a number of disadvantages in the current two-stage method, including impaired mobility, limited stability, impaired alignment, risk of dislocation and pain. As spacers are often made of cement, the articulating surfaces are rougher than the normal metal/plastics surfaces of primary TKR implants. Patients sometimes report feeling a ‘grating’ of the knee, leading to stiffness.

Re-implantation is often difficult because of arthrofibrosis and in approximately 20 per cent of patients a less than optimal result is achieved. The process can be hugely traumatic for the patient and can directly impact their personal, work and active life. Re-infection rates can be as high as 40 per cent and in some circumstances can lead to amputation [5, 6].

Surgeons often choose a primary knee replacement to act as a spacer because they better preserve the joint line and soft tissues and offer stability and mobility. Primary replacements may better fill the void during the six-week treatment period but they do not deliver antimicrobial affect and thus infection is not directly treated and is less likely to be eradicated.

 

The silver solution

The antimicrobial properties of silver have been well documented and indeed it is used in several medical implants including catheters and bone screws to reduce the risk of infection after surgery. Work by some of the current authors has also involved developing a SMART-HIP implant with a composite coating layer including anti-microbial silver [7].

Silver offers a benefit in that bacterial strains are less likely to become resistant to silver in the same way that they might with antibiotics. There are currently three main commercially available silver coating systems that are being used or tested in medical implants: Agluna (Accentus Medical), Mutars (Implantcast) and MicroSilver (Biogate). They offer the same main advantage of infection prevention and have similarities in their location of coating (non-articulating or fixation surfaces) and mechanism of release in the body (coating dissolution), see Table 1.

There are a number of differences in the method of coating, substrates used, the amount of silver and thickness of the coating. Additionally, these three coatings rely on dissolution for the release of silver ions, making it difficult to control dose and the rate at which the silver is released.

One solution is to coat the articulating surfaces, in this case for a TKR, the femoral condyles, such that the release of silver occurs by mechanical stimulation (joint articulation) in the form of wear as well as dissolution.

 

The Smart Spacer Project

The Smart Spacer project is co-funded by Innovate UK and industrial partners and aims to develop an effective solution to fighting infection using two-stage revision implants which have a novel silver coating applied. The overarching aim of this work is to reduce the rate of infection in joint replacements. This project is being run by a collaboration of surgeons and engineers from The Royal National Orthopaedic Hospital (RNOH), MatOrtho Ltd, University College London (UCL), Queen Mary University London (QMUL) and Wallwork, see Figure 5.

The primary Medial Rotation KneeTM [12] (MRK^TM, MatOrtho, Figure 6) is a well-proven TKR prosthesis with good results, and many surgeons use them as spacers in two-stage revision procedures. The project aims to enhance the MRK implant by applying a smart silver coating (Agilliant^®, Wallwork) to the articulating surfaces of the metal femoral component. The coated spacer is ‘smart’ as it releases doses of silver in response to the stimuli of movement as the patient is encouraged to start mobilisation (mechanical wear) and in response to the synovial environment (bio-tribocorrosion); the coating may also respond by releasing more silver in a lower pH-environment, typical of an infected environment. However this mechanism requires further understanding.

The MRK is particularly suitable for enhancement using a smart coating. It has a medial ball-in-socket design, which as it suggests has a single radius spherical medial condyle articulating in a conforming tibial geometry. With a fully conforming profile throughout flexion and large contact surface area, the design allows for near ‘normal’ kinematics and offers a high degree of stability. The total translation required to sublux the femur over the tibia is 31mm, which is greater than any other current TKR design, making it very difficult to dislocate (sublux) during anterior loaded activities; a key requirement for daily function (walking down stairs for example). These characteristics of the MRK are very important during the interim recovery period of an infected knee. The ability to keep the knee mobile, aligned and stable will reduce the likelihood of fibrous tissue forming and will optimise outcome in the second phase of replacement.

Several iterations of the coating architecture have been developed and applied by the coating expert partner Wallwork (EB-PAPVD, Wallwork Cambridge, UK). Chromium and silver in their pure metallic forms are evaporated under high vacuum conditions and a CrN-Ag Agillant coating is formed by introducing high purity nitrogen gas. This forms a highly wear–resistant surface with high levels of silver present.

The project involves accelerated knee simulator testing to determine the amount of silver released from Agillant coated MRK cobalt-chromium (CoCr) femoral components, articulating against a MRK ultra-high molecular weight polyethylene (UHMWPE) tibial components (Figure 7); this has not been done previously. Analysis of the wear debris generated during simulator testing is being analysed at QMUL to provide full characterisation of the particles and silver ions released.

Concurrently, a network of surgeon collaborators across England (Stanmore, Exeter, Nottingham, Watford and Leicester, Figure 8) are working to implant uncoated MRK components in suitable cases of patients requiring two-stage revisions for infections. Data on the speed of recovery and formation of biofilms will serve as a control arm for future clinical testing (after ethical approval) of MRK components that have been coated with the optimum silver coating identified during the pre-clinical simulator testing.

The knowledge gained from this study is being disseminated throughout the course of the project.

 

Conclusion

The TKR is the most common orthopaedic procedure performed in the UK. Infection-related complications in patients with TKRs is of growing concern, often requiring complex revision procedures. There is growing evidence that the traditional use of antibiotics to treat infection is becoming less effective due to an increase of antimicrobial resistance. The use of silver in medical implants has been demonstrated to be successful in fighting infection and may offer solutions for controlling infection cases in patients with TKRs. The authors of this article are developing and testing a novel ‘smart’ silver coating that is applied directly to the articulating surfaces of femoral knee components. This collaboration between industry, university and hospitals aims to produce a ‘silver solution’ that is more effective than traditional methods of treating infection.

 

References

1. National Joint Registry for England and Wales (NJR) 13th Annual Report. 2016. Available at www.njrcentre.org.uk
2. Patel A, Pavlou G, Mujica-Mota RE, Toms AD. 2015. The epidemiology of revision total knee and hip arthroplasty in England and Wales. Bone Joint J, 97-B(8): 1076-1081.
3. Kurtz S, Ong K, Lau E, Mowat F, Halpern M. 2007. Projections of primary and revision hip and knee arthroplasty in the United States from 2005 to 2030. J Bone Joint Surg Am, 89(4): 780-5.
4. No authors listed. Ortho tip: Spacer in two-stage revision in periprosthetic knee infection, Available at http://doctorbond.in/ortho-tip-spacer-in-two-stage-revision-in-periprosthetic-knee-infection/
5. Haddad FS, Masri BA, Campbell D, McGraw RW, Beauchamp CP, Duncan CP. 2000. The PROSTALAC functional spacer in two-stage revision for infected knee replacements. Prosthesis of antibiotic-loaded acrylic cement. J Bone Joint Surg, 82:807–12
6. Chun KC, Kim KM, Chun CH. 2013. Infection following total knee arthroplasty. Knee Surg Relat Res, 25(3): 93-99.
7. Tecvac Ltd. 2012. SMART-HIP research project: New coatings extend life of hip implants. Available at http://pressreleases.responsesource.com/news/73934/smart-hip-research-project-new-coatings-extend-life-of-hip-implants/
8. No authors listed. Agluna. Available at http://www.accentus-medical.com/products-agluna.asp
9. No authors listed. Silver coating. Available at http://www.implantcast.info/
10. No authors listed. With innovated antimicrobial technologies against infections. Available at http://bio-gate.de/en/
11. de Villiers D, Hothi H, Khatkar H, Meswania J, Blunn G, Skinner J, Hart A. 2015. Lessons from retrievals: Retrievals help understand the reason for revision of coated hip arthroplasties. Proc Inst Mech Eng H, 229 (11): 804-11
12. MatOrtho. 2017. The Medial Rotation Knee. Available at http://www.matortho.com/medical-professionals/medial-rotation-knee.aspx

 

Authors

Smart Spacer Project Team: Harry Hothi¹, Colin Esler², Andrew Toms³, Jon Phillips³, Tim Waters⁴, Ben Bloch⁵, Peter James⁵, Jonathan Miles⁶, Rob Pollock⁶, Jakub Jagiello⁶, James Donaldson⁶, Laura Richards⁷, Simon Collins⁷, Julia Shelton⁸, Jonathan Housden⁹, Laurent Espitalier⁹, Liuquan Yang⁹, Iva Hauptmannova⁶, Alister Hart^1,6

1.University College London,
2. Spire Leicester Hospital,
3. Exeter Knee Reconstruction Unit,
4. West Hertfordshire Hospitals NHS Trust,
5. Spire Nottingham Hospital,
6. Royal National Orthopaedic Hospital,
7. MatOrtho Ltd,
8. Queen Mary University of London,
9. Wallwork Cambridge