Therapeutic Efficacy of an Erythromycin-Loaded Coaxial Nanofiber Coating in a Rat Model of S. aureus-Induced Periprosthetic Joint Infection

Abstract

Implant surface nanofiber (NF) coatings represent an alternative way to prevent/treat periprosthetic joint infection (PJI) via local drug release. We developed and characterized a coaxial erythromycin (EM)-doped PLGA/PCL-PVA NF coating. The purpose of this study was to determine the efficacy of EM-NF coatings (EM0, no EM, EM100 (100 mg/mL), and EM1000 (1000 mg/mL) wt/wt) in a rat PJI model. A strong bond of the EM-NF coating to the surface of titanium (Ti) pins was confirmed by in vitro mechanical testing. Micro-computed tomography (mCT) analysis showed that both EM100 and EM1000 NF effectively reduced periprosthetic osteolysis compared to EM0 at 8 and 16 weeks after implantation. Histology showed that EM100 and EM1000 coatings effectively controlled infection and enhanced periprosthetic new bone formation. The bone implant contact (BIC) of EM100 (35.08%) was higher than negative controls and EM0 (3.43% and 0%, respectively). The bone area fraction occupancy (BAFO) of EM100 (0.63 mm²) was greater than controls and EM0 (0.390 mm² and 0.0 mm², respectively). The BAFO of EM100 was higher than that of EM1000 (0.3 mm²). These findings may provide a basis for a new implant surface fabrication strategy aimed at reducing the risks of defective osseointegration and PJI.

Keywords: coaxial nanofibers; drug release; erythromycin (EM); osteointegration; periprosthetic joint infection (PJI); rat model; surface coating.

Figure 1

Ex vivo mechanical testing using a porcine bone implantation model: (A) the mechanical testing set up; (B) Ti pins with EM-NF coatings after push in and pull out test. The broken areas of EM-NF coating after testing were marked by a black box (n = 3). (C) Comparison of push in and pull out forces of Ti pins with EM-NF coating (n = 3). * p < 0.05 between EM0 and EM100.

Figure 2

Measurement of periprosthetic osteolysis area (μm²). Comparison of osteolysis areas among groups at 8 weeks and 16 weeks. p = 0.08 between EM0 and EM100 groups at 16 weeks (n = 8 for each group and each time point).

Figure 3

H&E staining of paraffin sections of tibia samples 8 and 16 weeks, respectively, for EM-NFs groups after implantation (n = 5), in which bone area is referred to as the mature bone surrounding the Ti implant. NB, newly formed bones surrounding the Ti implants within 200 µm; black arrowheads, fibrous tissue; black stars, infection and inflammation area.

Figure 4

Toluidine blue staining of hard-tissue sectioning collected at 16 weeks after implantation for negative control, EM0, EM100, and EM1000 groups. Bone implant contact (BIC) and bone area fraction occupancy (BAFO) scores within 200 μm of the medullary implant (implant = yellow inner circle; 200 µm ROI from implant = yellow outer circle).

Figure 5

Measurement of periprosthetic osteolysis area. (A) µCT scan showing the position of Ti pin implantation. (B) Scanning through all slices from the segment under the pin head to the end of the pin was performed and a slice with the largest area of osteolysis was selected. A contour around the cortical bone is outlined, and the area of the contour (include units) is recorded. Pin area is constant and approximately 0.0064 cm².