Multilayer polypeptide nanoscale coatings incorporating IL-12 for the prevention of biomedical device-associated infections

Abstract

Biomedical device-associated infection is one of the most common and problematic complications faced by millions of patients worldwide. The current antibiotic therapy strategies face challenges, the most serious of which is antibiotic resistance. Studies have shown that the systemic level of interleukin 12 (IL-12) decreases following major injuries resulting in decreased cell-mediated immune response. Here we report the development of IL-12 nanoscale coatings using electrostatic layer-by-layer self-assembly nanotechnology. We found that IL-12 nanoscale coatings at the implant/tissue interface substantially decrease infections in vivo, and IL-12 nanoscale coatings are advantageous over traditional treatments. This approach could be a revolutionary step toward preventing device-associated infections using a non-antibiotic approach.

Figure 1

(a) A schematic diagram of the nanoscale coating structure. BSA, as a carrier of IL-12, was used as a coating component. PLL was used as a “glue” coating component. (b) Fluorescence labeled coating on a K-wire. (c) Formation of the multilayer nanoscale coating monitored by ellipsometry.

Figure 2

(a) Preparation of a nanoscale coating and (b-c) release of IL-12 from the coating. (a) coating absorbance vs. wavelength; the inset shows the amounts of IL-12 released from IL-12 nanoscale coatings of different coating structures. (b) IL-12 release vs. IL-12 concentration in the BSA solution at day 9. (c) IL-12 release vs. time; the inset shows the actual amounts of IL-12 released. Data shown is an average of three samples.

Figure 2

(a) Preparation of a nanoscale coating and (b-c) release of IL-12 from the coating. (a) coating absorbance vs. wavelength; the inset shows the amounts of IL-12 released from IL-12 nanoscale coatings of different coating structures. (b) IL-12 release vs. IL-12 concentration in the BSA solution at day 9. (c) IL-12 release vs. time; the inset shows the actual amounts of IL-12 released. Data shown is an average of three samples.

Figure 3

SEM images of nanoscale coatings on control samples (a and c) and after implantation (b and d).

Figure 4

Infection rate vs. IL-12 dose. Six rats were studied in each group and the control group was repeated once (total 36 rats). The different doses of IL-12 were obtained by manipulating the concentration of IL-12 loading solution and the number of coating layers, as shown in Figs. 2b and c.

Figure 5

Local IL-12 therapy stimulates Th cells to secrete Th1 cytokines. Via positive feedback, cell-mediated immunity can be promoted to battle bacteria such as S. aureus.