Antimicrobial Technology in Trauma and Spinal Implants

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Background
Antimicrobial Coated Implants
Photoactive-based coatings
Non-Coating Technology
Conclusion
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Background

Orthopedic implants are commonly used in spine surgery, arthroplasty, and arthrodesis, as well as for applications in treating fractures and nonunions. Typically formulated from titanium, stainless steel, cobalt-chromium, or polyethylene polymers, orthopedic implants can serve as niduses for infection and may hinder infection clearance due to biofilm formation on the implant surface. Orthopedic implant-associated infections are challenging complications that can lead to delayed healing, implant loosening, implant removal, amputation, or even death.

In many infections, bacteria will form a biofilm on the implant, increasing their resistance to antibiotics and resulting in infection persistence despite aggressive surgical debridement and prolonged antibiotic treatments. A biofilm is an aggregated mass of bacteria that can form on the surface of an orthopedic implant, providing the ideal environment for bacteria to flourish. Such bacterial growths are difficult to eliminate and present a serious challenge in implant development. In the United States, orthopedic implants are associated with an approximate 5% infection rate, representing 100000 infections per year.

This frequency represents a notable economic burden on both patients and healthcare providers. Healthcare Act figures are elusive, even with the existence of antibiotic prophylactic; it is estimated that implant infections increase the overall cost of hospitalization by up to 45% on average.

Antimicrobial Coated Implants

Current antimicrobial strategies have largely focused on coating-based approaches-each of which aims to prevent infection by mitigating biofilm formation. Key coatings include antibiotic, antiseptic, nano-silver, and photoactive-based coatings.

1. Antibiotic-based coatings

Common biocompatible drug carriers for the coatings include polymethylmethacrylate (PMMA), poly(lactic-co-glycolic acid) (PLGA), and poly(lactic acid). And Hydroxyapatite (HA) was recently shown to be an effective drug carrier of gentamicin.

However, the limitations of antibiotic coatings include the use of fixed, predetermined antibiotics; limited duration of drug elution; and the risk of developing drug resistance.

2. Antiseptic-based coatings

In contrast to antibiotic coatings, which are formulated to work against specific bacterial strains, antiseptic-based coatings are intended to combat a wide range of bacteria by way of more general chemical agents. For this reason, antiseptic coatings are less likely to induce bacterial resistance compared to antibiotics. But due to their broad-spectrum efficacy, antiseptic-based coatings have some level of generalized toxicity. Because of their general toxicity, antiseptic-based coatings are more commonly utilized as topical dressings.

3. Chitosan coatings

Chitosan is a polymer of chitin that exhibits active anti¬microbial properties. Recent pre-clinical studies have provided evidence that several composites of chitosan may act as effective antimicrobial agents suited for titanium orthopedic implants. Studies have suggested that chitosan alone may not be sufficiently potent as an antimicrobial agent and suffers from poor release kinetics.

4. Nano-silver coatings

The antimicrobial properties of silver particles are well-established. Silver particles have several known mechanisms of action, including binding to thiol groups of enzymes, cell membranes, and nucleic acids, resulting in structural abnormalities, a damaged cell envelope, and inhibition of cell division. Silver nanoparticles are typically incorporated into titanium surfaces or polymeric coating to control the release rate and duration of the bioactive silver. Electrical currents are established when silver nanoparticles (cathode) embedded in a titanium matrix (anode) are exposed to electrolytes – this galvanic coupling can cause changes in bacterial membrane morphology and DNA, leading to cell death. Silver-based coatings have antimicrobial efficacy against a broad spectrum of pathogens, including Escherichia coli, S. aureus, and S. epidermidis.

Because of its long history of usage and relatively low toxicity, silver-based antimicrobial coatings represent a very promising tool against antibiotic-resistant pathogens. The effectiveness of the technology has been shown to be largely dependent on the ability of the coating matrix to provide efficacious release kinetics and formulation of silver nanoparticles or ions.

Photoactive-based coatings

The Photoactive-based coating is composed of titanium alloy, and after being activated by ultraviolet radiation, it exerts a bactericidal effect through film degradation. Titanium dioxide (TiO2) has become commonly used in photoactive-based coatings due to its strong oxidizing ability, non-toxicity, and long-term chemical stability. The TiO2-based photosensitive coating is resistant to mechanical stress, has antimicrobial efficacy against S. aureus and S. epidermidis cultures, and has the added advantages of low cost and easy scalability.

Non-Coating Technology

1. Antibiotic-loaded bone cement

In addition to coatings, several other antimicrobial orthopedic implant technologies are being evaluated. Antibiotic-loaded bone cement (ALBC), such as PMMA, is widely used by orthopedic surgeons to help secure arthroplasty implants, fill bone voids, and treat vertebral compression fractures. ALBC has been in use since first being developed in 1970 as a potential method for in situ drug release. Due to the irregular release of antibiotics, only 5%-8% of the drug typically elutes properly. Therefore, the high doses needed for a therapeutic effect have been shown to produce pathogen resistance.

2. Modified surface characteristics

Modifying implant surface characteristics has also been investigated as a means of reducing biofilm. For example, mixtures of polyethylene oxide and protein-repelling polyethylene glycol have shown significant bacterial inhibition when applied to implant surfaces. Surface characteristic modification has been shown to interfere with the osseointegration of the implants, challenging its clinical application. Some studies have shown that certain pathogens are able to adhere, proliferate, and form biofilms more readily on rough surfaces. The data available suggest there is a threshold where modified surface microtopography can be an effective means of reducing biofilm or encouraging bacterial growth.

3. Electrospinning

Electrospun matrices of PLGA nano-fibers have recently been proposed as a promising antimicrobial approach to orthopedic implant-associated infections. In electrospinning, ultrafine fibers with nanometer diameters form a matrix with a very high surface-area-to-volume ratio. Produced by syringe-pumping various drug and polymer solutions in the presence of a high electrical field potential, the resulting drug-loaded, non-woven PLGA membranes are flexible and porous, and enable controlled drug release. Like coating, the matrices adhere directly to orthopedic implants.

Conclusion

Several imperfect options exist for reducing the risk of orthopedic implant infections. Despite technological advancement, orthopedic implant-associated infections remain an important clinical problem, necessitating additional improvement. With promising technology on the horizon, it seems that the answer for reduced infection may not lie solely in one device or technology but in the synergy of many.