Remote Eradication of Bacteria on Orthopedic Implants via Delayed Delivery of Polycaprolactone Stabilized Polyvinylpyrrolidone Iodine

Abstract

Bacteria-associated late infection of the orthopedic devices would further lead to the failure of the implantation. However, present ordinary antimicrobial strategies usually deal with early infection but fail to combat the late infection of the implants due to the burst release of the antibiotics. Thus, to fabricate long-term antimicrobial (early antibacterial, late antibacterial) orthopedic implants is essential to address this issue. Herein, we developed a sophisticated MAO-I₂-PCLx coating system incorporating an underlying iodine layer and an upper layer of polycaprolactone (PCL)-controlled coating, which could effectively eradicate the late bacterial infection throughout the implantation. Firstly, micro-arc oxidation was used to form a microarray tubular structure on the surface of the implants, laying the foundation for iodine loading and PCL bonding. Secondly, electrophoresis was applied to load iodine in the tubular structure as an efficient bactericidal agent. Finally, the surface-bonded PCL coating acts as a controller to regulate the release of iodine. The hybrid coatings displayed great stability and control release capacity. Excellent antibacterial ability was validated at 30 days post-implantation via in vitro experiments and in vivo rat osteomyelitis model. Expectedly, it can become a promising bench-to-bedside strategy for current infection challenges in the orthopedic field.

Keywords: antibacterial coating; micro-arc oxidation; orthopedic implants; polycaprolactone; povidone-iodine.

Figure 1

Schematic route and surface characteristics of the MAO-I₂-PCLx coatings (x = 1, 2, 3). The illustrative diagrams of the preparation process (A), SEM morphology (B), and EDS mapping (B) of iodine-carrying PCL-controlled release coating.

Figure 2

Chemical composition and surface roughness of the coatings: (A) XPS results about the survey spectrum of MAO coating; (B–E) the corresponding core-level spectra for Ti 2p, C 1s, O 1s of MAO coating; (F) XPS results about the survey spectrum of MAO-I₂ coating; (G–J) the corresponding core-level spectra for Ti 2p, C 1s, O 1s of MAO-I₂ coating; (K) the AFM images of the titanium and MAO-I₂-PCLx coatings (x = 1, 2, 3).

Figure 3

The time-dependent iodine release curve and iodine content determination of the coatings: (A) schematic diagram for the iodine release of coating; (B) ICP determination and analysis of the cumulative release content in Tris buffer at different time points; (C) cell biocompatibility test of different coatings; and (D) cytoskeleton staining after 3 days of BMSC growth on the coatings. * denotes p < 0.05.

Figure 4

The antibacterial activities of the coatings through a three-day exposure to S. aureus and E. coli: (A,B) the SEM micrographs of cultured bacteria on the surface of coatings (yellow arrows represent the depressed S. aureus and red arrows represent the depressed E. coli); (C,D) live/dead confocal images showing the live or dead bacteria on the coatings (green represents the live bacteria and red represents the dead bacteria).

Figure 5

Antibacterial experiments of corresponding substrates at different time points in vitro: (A) inhibition zone experiment of different samples of S. aureus; (B) colonies of S. aureus and E. coli were cultivated on the corresponding surfaces of samples at different time points.

Figure 6

Antibacterial effect of the corresponding substrates in vivo: (A) scheme of implantation process of implanting a titanium rod in the femur; (B) the infected rat femur images 7 days after the implantation of the titanium rod; (C) H&E, Gram, and Masson staining images in the regions of femur osteoepiphysis with different samples implantation, respectively; blue arrows represent lymphocytes and neutrophils infiltration, red circles represent inflammatory cells and bacteria, and black arrows represent collagenous fibers.

Figure 7

Transformation effect of orthopedic implants with the antibacterial performance: (A–C) general observation of pedicle screws (PS), locking screws (LS), and locking compression plate (LCP); (D) the surface morphology and EDS mapping of iodine element; (E) SEM morphology of S. aureus and E. coli culturing on the surface of the LCPs; (F) spread plate images of S. aureus and E. coli seeding on the surface of the LCPs.