Can a 'smart' coating on titanium reduce the risk of infection?

In Vivo Efficacy of a "Smart" Antimicrobial Implant Coating.


These authors explored the use of a "smart" implant coating that combines passive elution of antibiotic with an active-release mechanism that "targets" bacteria in an in vivo mouse model of post-arthroplasty infection.

They designed a biodegradable coating using branched poly(ethylene glycol)-poly(propylene sulfide) (PEG-PPS) polymer to deliver antibiotics both passively and actively. This  PEG-PPS polymer coating can be covalently linked to metal implants.

They used high-performance liquid chromatography (HPLC) quantification to study in vitro release kinetics in conditions representing (a) the physiologic environment and (b) the more oxidative, hyperinflammatory environment of periprosthetic infection. 

They tested the in vivo efficacy of the PEG-PPS coating delivering vancomycin and tigecycline using an established mouse model of post-arthroplasty infection consisting of a medical-grade, 0.8-mm-diameter titanium Kirschner-wire implant, precoated with PEG-PPS, PEG-PPS encapsulating vancomycin, or PEG-PPS encapsulating tigecycline, was surgically placed into the distal aspect of the right femur of the mice, and the joint was challenged with bioluminescent S. aureus Xen36 strain.

They used noninvasive bioluminescence imaging to quantify the bacterial burden; radiography to assess osseointegration and bone resorption; and implant sonication for colony counts.

In vitro-release kinetics confirmed passive elution above the minimum inhibitory concentration (MIC). A rapid release of antibiotic was noted when challenged with an oxidative environment (p < 0.05), confirming a "smart" active-release mechanism. 

The PEG-PPS coating with tigecycline significantly lowered the infection burden on all days, whereas PEG-PPS-vancomycin decreased infection on postoperative day (POD) 1, 3, 5, and 7 (p < 0.05). 

A mean of 0, 9, and 2.6 × 10(2) colony-forming units (CFUs) grew on culture from the implants treated with tigecycline, vancomycin, and PEG-PPS alone, respectively, and a mean of 1.2 × 10(2), 4.3 × 10(3), and 5.9 × 10(4) CFUs, respectively, on culture of the surrounding tissue (p < 0.05).

Implants coated with PEG-PPS alone showed a dramatic degree of periprosthetic osteolysis that became evident by POD 7 and progressed over time. In contrast, antibiotic encapsulated  PEG-PPS implants showed no detectable radiographic periprosthetic osteolysis. 

At 28 days, the control PEG-PPS coated implant was surrounded by osteolytic bone

 in contrast to the implants with tigecycline containing coating

They concluded that PEG-PPS coating provides a promising approach to preventing periprosthetic infection. This polymer is novel in that it combines both passive and active antibiotic-release mechanisms. The tigecycline-based coating outperformed the vancomycin-based coating in this study.

Comment: These authors emphasize the importance of preventing bacteria-containing biofilms on the surfaces of implants. They point to the short-lived effects of topical antibiotics as well as the disadvantages of antibiotic-impregnated cement (polymethylmethacrylate [PMMA]) with a poorly regulated erratic antibiotic release leaving an inert permanent surface for colonization. As an alternative, they pursued a completely biodegradable polymer coating that delivered antibiotics passively and actively stimulated by the reactive oxygen cased initiated by the presence of bacteria.

The authors remind us that at this point their studies have been limited to infection with S. Aureus and not against our 'favorite' bug, Propionibacterium.

Nevertheless they are addressing the key issue of hitting the bacteria before they have a chance to form a biofilm on titanium implants as discussed in this recent post:

Infections with Propionibacterium - the necessity of a surgical implant

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The procedure and its influence on the outcome

Many implant systems are available for the management of shoulder arthritis. Each has its particular features, some of which affect the risk of failure. Here are some posts related to implant design and insertion technique.

Impaction graft fixation of the humeral component - our approach
Long stem humeral components

Arthrosurface
Resurfacing
Cementless surface replacement

Total shoulder vs hemiarthroplasty
Total shoulder vs hemiarthroplasty

Insertion of the glenoid component - our approach
Insertion of the glenoid component - our approach
Insertion of the glenoid component - our approach
Avoiding heat damage to the glenoid bone
Glenoid cément technique

Pegged vs keeled glenoid components and glenoid version
Pegged vs keeled glenoid components
Keeled glenoids
Keeled glenoids
Convex-back cemented keel glenoid

Total shoulder with bone graft

Metal backed glenoid
Metal backed glenoid
Metal backed glenoid
Metal backed glenoid
Metal backed gleaned
Metal backed glenoid
Metal backed glenoid

Biological resurfacing
Biological resurfacing
Biological resurfacing
Biological resurfacing
Biological resurfacing
Biological resurfacing
Biological resurfacing

Reverse total shoulder
Reverse total shoulder
Reverse total shoulder
Reverse total shoulder
Reverse total shoulder
Reverse total shoulder
Reverse total shoulder
Reverse total shoulder
Reverse total shoulder
Reverse total shoulder
Reverse total shoulder
Reverse total shoulder
Reverse total shoulder
Reverse total shoulder
Stemless reverse total shoulder

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You may be interested in some of our most visited web pages including:shoulder arthritis, total shoulder, ream and run, reverse total shoulder, CTA arthroplasty, and rotator cuff surgery as well as the 'ream and run essentials'

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What drives the cost of joint replacements in the U.S.? : opinion of the New York Times

The cost of artificial joint replacements was the topic of a recent article in the New York Times.
While there can be much discussion about each of the points made, such as 'sticky pricing', the article is definitely worth a read.

In the spirit of making health care affordable for individuals and for the United States, all involved need to assure that the costs of implants, which comprise so much of the cost of having a joint replacement surgery, are appropriate. As the article points out, when an implant is established, the costs of its development should be recovered in a reasonable period of time and the price should fall. This does not seem to be happening.

Read and ponder.

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Variability in Costs Associated with Total Hip and Knee Replacement Implants. JBJS

Variability in Costs Associated with Total Hip and Knee Replacement Implants. JBJS

The authors point out that the average implant cost per case varied by over 600% ($1797 to $12093) for total knee replacement procedures and by over 400% ($2392 to $12651) for total hip replacement procedures.  These wide variances could not be explained by differences in patient characteristics. The ratio of device cost to total surgical cost for knee and hip arthroplasty can be as high as 87%, with the median ratio being 43%.

The authors point out that data are currently lacking to support the belief that higher cost devices are associated with better outcomes. This is an important article, especially when viewed in the light of the survivorship of some of the more expensive and 'more modern' implants as also shown here. On this basis some have advocated device regulation to assure that new technology is optimally applied.

While we are not aware of similar data for shoulder implants, it is logical to assume that the same phenomenon exists there. We have also seen that the results with newer shoulder implants may not justify the associated expense. Determination of differences in outcome may require quite long term followup.

An interesting commentary on this article was offered: Joint Replacement Costs in the Era of Healthcare Reform: Commentary on an article by James C. Robinson, PhD, MPH, et al.: “Variability in Costs Associated with Total Hip and Knee Replacement Implants” The author of this commentary reminded that orthopaedic implants and procedures are major contributors to the rising cost of healthcare. In spite of the rising number of these procedures performed each year, the cost of these procedures is not following 'economies of scale principles' in which the implant cost per case would drop as the number of cases increased. The author of the commentary suggests several possible approaches to reducing these costs: (1) collective bargaining by Medicare with the implant manufacturers, (2) defining standards on the impact of new devices on cost and outcomes before they come to market, opining that 'there is little evidence that newer and more expensive devices are associated with better functional outcomes', (3) lack of  'gain-sharing' between medical centers and surgeons, which could incentivize surgeons to cut costs without compromising outcomes, and (4) lack of a national joint registry, such as those that exist in other countries, that would provide cost and outcomes data that could inform future decisions on implant selection for particular categories of patients.

The bottom line is that in future we need to pay more attention to the value equation: how much better are the documented results with the new implant divided by how much more it costs than the existing device? If a country wanted to curb the rising cost of joint arthroplasty, would it be better for it to reduce the cost of implants or to reduce the payments to the surgeons implanting them? That choice may be on us sooner rather than later.

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