Selenium nanoparticles as anti-infective implant coatings for trauma orthopedics against methicillin-resistant Staphylococcus aureus and epidermidis: in vitro and in vivo assessment

Background

Infection is a leading complication following implantation of fixation devices for traumatic orthopedic injuries.^1–4 Traumatic wounds, such as those resulting from accidents, military combat and/or training, often involve extensive tissue damage in highly contaminated environments.⁵ Effective infection control is known to be key in the healing and rapid recovery of injuries in such cases.⁶ Despite clinically effective debridement and antibiotic treatment for these injuries, the infection rates remain as high as 15% and 20% in traumatic extremity injuries and abdominal wounds, respectively.^7,8 The introduction of a medical device to treat the wound and/or restore anatomic integrity can provide much needed benefits but comes with the risk of infection. Additionally, the relative immunosuppression following trauma may potentiate the growth of either contaminating bacteria or hospital-acquired infection. Multidrug-resistant bacteria such as Acinetobacter baumannii, Pseudomonas aeruginosa, extended-spectrum β-lactamase-producing Klebsiella species, Escherichia coli, and methicillin-resistant Staphylococcus strains have been found in these infected wounds,^7,8 especially in patients who have multitrauma and prolonged stay in intensive care units. The presence of medical devices has been associated with the formation of biofilms (ie, bacteria-containing polysaccharide matrices that are extremely resistant to host defenses and antibiotic treatment).^9–11 Biofilm-related device-associated infections have been shown to be a cause of both implant failure, reoperation, and even death.^12,13

In the last few decades, new strategies have been developed to tackle the problems of bacterial drug resistance and biofilm formation. These strategies can be roughly divided into two categories: controlled delivery of antibiotics and development of non-drug antimicrobial materials. The antibiotic delivery approach aims to specifically target high doses of drug molecules to the infection sites, limiting sub-lethal doses and/or non-specific exposure of bacteria to the drugs to combat further development of antibiotic resistance.^14–16 Delivery strategies to improve drug penetration into bacterial biofilms are also being actively investigated.¹⁶ In the second category, new antimicrobial agents which do not contain antibiotics are being developed. Examples of this include metallic/ceramic nanoparticles (NPs) (such as silver, copper oxide, zinc oxide, gold, titanium dioxide, etc.),^17–20 polymeric materials (such as chitosan²¹), quaternary ammonium compounds,^22,23 and antimicrobial peptides.²⁴ Surface modification to repel bacteria or kill on contact is also a promising approach.^25,26 Nano-topography...