Antimicrobial activity of bone cements embedded with organic nanoparticles

Abstract

Infections after orthopedic surgery are a very unwelcome outcome; despite the widespread use of antibiotics, their incidence can be as high as 10%. This risk is likely to increase as antibiotics are gradually losing efficacy as a result of bacterial resistance; therefore, novel antimicrobial approaches are required. Parabens are a class of compounds whose antimicrobial activity is employed in many cosmetic and pharmaceutical products. We developed propylparaben nanoparticles that are hydrophilic, thus expanding the applicability of parabens to aqueous systems. In this paper we assess the possibility of employing paraben nanoparticles as antimicrobial compound in bone cements. The nanoparticles were embedded in various types of bone cement (poly(methyl methacrylate) [PMMA], hydroxyapatite, and brushite) and the antimicrobial activity was determined against common causes of postorthopedic surgery infections such as: Staphylococcus aureus , methicillin-resistant S. aureus , Staphylococcus epidermidis , and Acinetobacter baumannii . Nanoparticles at concentrations as low as 1% w/w in brushite bone cement were capable of preventing pathogens growth, 5% w/w was needed for hydroxyapatite bone cement, while 7% w/w was required for PMMA bone cement. No detrimental effect was determined by the addition of paraben nanoparticles on bone cement compression strength and cytocompatibility. Our results demonstrate that paraben nanoparticles can be encapsulated in bone cement, providing concentration-dependent antimicrobial activity; furthermore, lower concentrations are needed in calcium phosphate (brushite and hydroxyapatite) than in acrylic (PMMA) bone cements. These nanoparticles are effective against a wide spectrum of bacteria, including those already resistant to the antibiotics routinely employed in orthopedic applications, such as gentamicin.

An Injectable Hydrogel as Bone Graft Material with Added Antimicrobial Properties

“…11 ) as the apparent lag phase is typical of cell suspensions with high initial concentration. 36 , 39 , 40 However, when Sr was added to the hydrogel formulation, both bacteria displayed lag phases about 2 h longer; this difference was statistically significant ( p < 0.05) and corresponded to a reduction >90% (1 log 10 ) of the bacteria. The addition of Zn, on the other hand, had a similar effect on S. epidermidis , but smaller on MRSA; moreover, no synergistic effect between Sr and Zn was detected as apparent lag phase durations were not statistically different in case of Sr alone or Zn alone ( p < 0.05).…”

“…The lower the cell concentration on the sample in contact with the material, the longer the apparent lag phase (time required for the cell to grow to the threshold concentration of detection through turbidity); furthermore, assuming a doubling time of 30 min, an increment in apparent lag phase of 1.5 h is equivalent to a reduction of cell concentration of 1 log 10 because log 2 10 = 3.3. 36 Evidence of lethal activity against pathogenic bacteria was observed ( Fig. 11 ).…”

“…4 ) were encouragingly high for hydrogels. They exhibited similar rheological properties to PMMA bone cement 36 or to mineralized acrylate-based hydrogels through reaction–diffusion methods resulting in the formation of beta-TCP inside the hydrogel matrix. 33 Hence, they are likely to be suited for implantation in load-bearing sites.…”

“…The antimicrobial activity of the most promising hydrogels (with 20% v/v of 1,4-butanediol diacrylate), as seen before, was tested against S. epidermidis and MRSA. Both bacteria tested are common sources of postorthopedic surgeries 36–38 ; practically, no antimicrobial activity was exhibited by hydrogels not containing either Sr or Zn ( Fig. 11 ) as the apparent lag phase is typical of cell suspensions with high initial concentration.…”

“…The different response of these two species related to the intrinsic susceptibility of such bacteria and expected as MRSA is usually more resistant than S. epidermidis to antimicrobial agents. 36 , 39 , 40 …”