A rapid-release pure iodine coating on titanium implants to mitigate acute periprosthetic infections

Abstract

Background: Periprosthetic infections remain a significant challenge in orthopedic surgeries, primarily due to bacterial biofilm formation on implant surfaces. To address this issue, we developed a novel iodine-based coating on titanium implants designed to rapidly release iodine, thereby preventing acute infections. The efficacy and safety of this coating were assessed through both in vitro experiments and an in vivo rabbit model.

Methods: The iodine coating was applied to titanium implants using electrophoretic deposition. The coated implants were characterized using scanning electron microscopy (SEM), X-ray fluorescence spectroscopy (XRF), and energy-dispersive spectroscopy (EDS). In vitro studies included antibacterial assays, iodine release kinetics, and hemolysis tests. Additionally, an acute periprosthetic infection model in rabbits was established to evaluate the coating's performance in vivo.

Results: The electrophoretic deposition technique successfully produced a uniform iodine coating with high iodine content and rapid release kinetics. In vitro tests demonstrated significant antibacterial activity against Staphylococcus aureus and Escherichia coli. The rabbit model showed a marked reduction in infection rates compared to uncoated implants, with no adverse effects on bone integration.

Conclusion: This study introduces a promising iodine-based coating for titanium implants, offering a rapid and effective solution to prevent acute periprosthetic infections while maintaining biocompatibility and supporting bone healing.

Keywords: biofilm prevention; infections; iodine; orthopedic implants; titanium.

FIGURE 1

Appearance and microscopic analysis of the titanium needle. (B) Macroscopic view of titanium needle (3.0 cm in length, 2.0 mm in diameter, Ti-6Al-4V alloy): The uncoated titanium needle exhibits a golden-yellow surface, whereas the iodine-coated needle has a brown surface. Scanning electron microscope examination showing that (A) the uncoated titanium needle exhibits scattered scratches on its surface; (C) the iodine-coated titanium needle shows a dense coating with a uniform structure.

FIGURE 2

The XRF analysis results demonstrated the successful loading of iodine. The surface coating exhibited the highest elemental composition of titanium (47.29 wt%), oxygen (33.45 wt%), iodine (13.85 wt%), and aluminum (3.06 wt%). XRF, X-ray fluorescence spectroscopy.

FIGURE 3

Outcomes of EDS analysis, revealing a uniform distribution of iodine and other elements across the surface of the iodine coating without any observed aggregation or shedding phenomena. EDS, energy dispersive spectrometry.

FIGURE 4

In vitro bacterial culture. The plate colony-forming unit (CFU) count of the Staphylococcus aureus standard strain in the control group (TI) and experimental group (TI-I) was 163.20 ± 21.54 and 57.70 ± 20.91, respectively, demonstrating statistical significance (*P < 0.05). For Escherichia coli standard strain, the plate CFU count was 131.70 ± 25.87 and 34.60 ± 19.60 in the control group (TI) and experimental group (TI-I), respectively, showing a significant difference (**P < 0.05). 11.67 wt.%.

FIGURE 5

Release of iodine in vitro. The initial iodine content was 13.85 wt.%, which decreased to 11.67 wt.% on day 3, further declined to 8.17 wt.% on day 7, and subsequently decreased to 2.14 wt.% on day 14.

FIGURE 6

Hemolysis rate of red blood cells in model rabbits. The hemolysis rates of the ordinary titanium needles and iodine-coated titanium needles were 1.8% and 2.6%. Normal saline served as a negative control with a hemolysis rate of 0%, whereas the positive control using 1% TritonX-100 exhibited a hemolysis rate of 100%.

FIGURE 7

Microbial culture and statistical analysis. In the control group (TI), nine samples tested positive whereas one sample tested negative. Conversely, in the experimental group (TI-I), only one sample showed positive results with nine samples testing negative (*P < 0.05).

FIGURE 8

Histopathological features (magnification*40). (A) A prominent mass infiltration of neutrophils was observed, leading to local aggregation and formation of microabscesses, accompanied by bone destruction and fibrotic changes. (B) The bone tissue exhibited overall normal characteristics with no apparent inflammatory cell infiltration observed; however, mild fibrotic changes were noted. (C) Statistical analysis revealed a significant difference between the two groups (*P < 0.05). (A) needle track; (B) bone trabeculae and bone cells; (C) bone matrix. TI, control group, TI-I, experimental group.

FIGURE 9

Morphology and statistical analysis of bacterial adhesion on implant surfaces. Scanning electron microscopy (magnification*5,000) revealed the following observations. (A) Staphylococcus aureus adhesion exhibited mostly irregular scattered and isolated distribution. (B) A significant number of Staphylococcus aureus formed clusters, displaying irregular shapes and local fusion into sheets. (C) No adhesion of Staphylococcus aureus was observed on the surface of the titanium needle. (D) Statistical analysis demonstrated a significant difference between the two groups, with *P < 0.05. TI, control group, TI-I, experimental group.

FIGURE 10

Laser confocal microscopy. (A) The control group exhibited a substantial number of densely distributed green fluorescence and sparsely scattered red fluorescence on the surface of Kirschner needles. (B) In the experimental group, iodine-coated titanium needles predominantly displayed a sparse distribution of red fluorescence with occasional small clusters of green fluorescence.

FIGURE 11

Infection rate. In the control group (TI), there were nine cases of infection, yielding an infection rate of 90%, while in the experimental group (TI-I), there were two cases of infection with an infection rate of 20%. The comparison between the two groups showed a statistically significant difference, *P < 0.05.

FIGURE 12

Morphology of metaphyseal bone cells. Transmission electron microscopy (magnification*5,000): (A) The bone matrix exhibited a high number of vacuoles with low density, aberrant morphology of bone cells, absence of bone tubules and cell processes, and reduced relative volume of the nucleus. (B) The bone matrix displayed uniform density, normal shape of bone cells, presence of bone tubules and cell processes, plump nuclei, and abundant contents.