Cefazolin embedded biodegradable polypeptide nanofilms promising for infection prevention: A preliminary study on cell responses

Abstract

Implant-associated infection is a serious complication in orthopedic surgery, and endowing implant surfaces with antibacterial properties could be one of the most promising approaches for preventing such infection. In this study, we developed cefazolin loaded biodegradable polypeptide multilayer nanofilms on orthopedic implants. We found that the amount of cefazolin released could be tuned. A high local concentration of cefazolin was achieved within the first a few hours and therefore may inhibit bacterial colonization in the critical post-implantation period. The developed cefazolin loaded nanofilms showed their in vitro efficacy against Staphylococcus aureus (S. aureus); the more antibiotics loaded, the longer the nanocoated implant had antibacterial properties. More interestingly, antibiotic-loaded polypeptide multilayer nanofilms also improved osteoblast bioactivity including cell viability and proliferation. These findings suggested that biodegradable polypeptide multilayer nanofilms as antibiotic carriers at the implant/tissue interface are compatible with human cells such as osteoblasts and bactericidal to bacteria such as S. aureus. These characteristics could be promising for preventing implant-associated infection and potentially improving bone healing.

Effect of various concentrations of antibiotics on osteogenic cell viability and activity

“…Despite the difference in treatment duration between the current and previous studies, our data are consistent with several other studies in which shorter time periods were used and/or difference cell types were studied. 12,14,15,[17][18][19][20][21][22][23] This similarity both adds validity to our data and suggests that the negative effects imparted by high levels of antibiotics in this study may be a result of changes that occur at early time points.…”

“…For example, the cephalosporin cefurotoxime has the potential to increase ALP activity and proliferation, 23 and a cefazolin-loaded biodegradable polypeptide multilayer nanofilm improved osteoblast viability and proliferation. 12 Although we did not use the same doses as others for the cephalosporins, and although not significant, we observed a trend for increases in ALP activity for the cephalosporins as well (Fig. 2D-F).…”

“…With an improved understanding and application of growth factors to improve bone regeneration, dual-delivery implants, implants that deliver both a growth factor and antimicrobial, may present a means to simultaneously promote bone growth and prevent infection. Arguably, biocompatible and bioabsorbable carriers that can deliver growth factors to improve bone regeneration [6][7][8][9] and antibiotics to prevent infection 8,[10][11][12][13] from the same implant may be superior therapeutics in the context of severe open fractures.…”

Nanotechnology applications in osteodistraction

“…[21] Different surface modifications and coating techniques can be used, such as direct impregnation with antibiotics and immobilization of an antimicrobial agent in a matrix capable of binding to different surfaces, [22] as well as coating with antimicrobial, active metals such as copper and silver, [23] nitric oxide-releasing materials [24] and titanium dioxide films. [25] Ainslie et al [26] have shown in vitro that nanostructured surfaces display reduced inflammation in comparison with a respective flat control.…”

“…Li et al [21] developed biodegradable polypeptide multilayer nanofilms to potentially serve as antibiotic carriers at the implant-tissue interface. They demonstrated that polypeptide multilayer nanofilms, with or without cefazolin, have antibacterial activity against organisms frequently associated with osteomyelitis, and may improve bone healing through improving osteoblast cell adhesion, viability, and proliferation.…”