Saturday, November 12, 2016

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