Recent advances in thromboresistant and antimicrobial polymers for biomedical applications: just say yes to nitric oxide (NO)

Abstract

Biomedical devices are essential for patient diagnosis and treatment; however, when blood comes in contact with foreign surfaces or homeostasis is disrupted, complications including thrombus formation and bacterial infections can interrupt device functionality, causing false readings and/or shorten device lifetime. Here, we review some of the current approaches for developing antithrombotic and antibacterial materials for biomedical applications. Special emphasis is given to materials that release or generate low levels of nitric oxide (NO). Nitric oxide is an endogenous gas molecule that can inhibit platelet activation as well as bacterial proliferation and adhesion. Various NO delivery vehicles have been developed to improve NO’s therapeutic potential. In this review, we provide a summary of the NO releasing and NO generating polymeric materials developed to date, with a focus on the chemistry of different NO donors, the polymer preparation processes, and in vitro and in vivo applications of the two most promising types of NO donors studied thus far, N-diazeniumdiolates (NONOates) and S-nitrosothiols (RSNOs).

Antimicrobial nitric oxide releasing surfaces based on S-nitroso-N-acetylpenicillamine impregnated polymers combined with submicron-textured surface topography

“…44,45 Furthermore, a problem with many similar bactericidal surfaces is the attachment of dead microorganisms remaining on the antibacterial coating, which can trigger immune response and inflammation, as well as block a coating’s active functional groups. 3 A unique attribute of NO releasing materials is that they can significantly reduce bacterial adhesion and prevent mature biofilm formation when released from the biomaterial surface, even at very low concentration. This may allow the bacteria to be susceptible to conventional antibiotics treatment and improve patient outcomes.…”

“…1–3 Such infections are extremely difficult to treat by use of antibiotics alone due to biofilm formation on the surface of the devices. Microbial biofilm consists of extracellular polymeric substances (EPS) that are known to be a physical barrier that protects bacteria from traditional antibiotic treatment.…”

“…3,17–21 Nitric oxide serves as a potent antimicrobial agent in our body’s immune response system to combat infectious diseases. 21–23 NO possesses broad-spectrum antimicrobial/bactericidal activity against both gram-positive and gram-negative bacteria, including methicillin-resistant S. aureus (MRSA), without any known resistance.…”

Inhibition of bacterial adhesion and biofilm formation by dual functional textured and nitric oxide releasing surfaces

“…It has not been reported that NO treatment would cause potential antibiotic resistance. [50] Therefore, the controlled release of NO over a long period (>10 d) is desirable and will provide additional benefits for the long-term success of polymeric implants.…”

Innovative Modifications for Preventing Mesh Infections

“…These effects are the result of oxidative and nitrosative stress generated by reactive intermediates of nitric oxide, resulting in damage to DNA, proteins and cell membranes. Nitric oxide is metabolized very rapidly by human metabolism in order to prevent toxicity [104,105]. In a study by Engelsman et al, monofilament polypropylene mesh was coated with a low concentration NO-releasing carbon-based coating.…”