Understanding long-term silver release from surface modified porous titanium implants

Abstract

Prevention of orthopedic device related infection (ODRI) using antibiotics has met with limited amount of success and is still a big concern during post-surgery. As an alternative, use of silver as an antibiotic treatment to prevent surgical infections is being used due to the well-established antimicrobial properties of silver. However, in most cases silver is used in particulate form with wound dressings or with short-term devices such as catheters but not with load-bearing implants. We hypothesize that strongly adherent silver to load-bearing implants can offer longer term solution to infection in vivo. Keeping that in mind, the focus of this study was to understand the long term release study of silver ions for a period of minimum 6months from silver coated surface modified porous titanium implants. Implants were fabricated using a LENS™ system, a powder based additive manufacturing technique, with at least 25% volume porosity, with and without TiO₂ nanotubes in phosphate buffer saline (pH 7.4) to see if the total release of silver ions is within the toxic limit for human cells. Considering the fact that infection sites may reduce the local pH, silver release was also studied in acetate buffer (pH 5.0) for a period of 4weeks. Along with that, the osseointegrative properties as well as cytotoxicity of porous titanium implants were assessed in vivo for a period of 12weeks using a rat distal femur model. In vivo results indicate that porous titanium implants with silver coating show comparable, if not better, biocompatibility and bonding at the bone-implant interface negating any concerns related to toxicity related to silver to normal cells. The current research is based on our recently patented technology, however focused on understanding longer-term silver release to mitigate infection related problems in load-bearing implants that can even arise several months after the surgery.

Statement of significance: Prevention of orthopedic device related infection using antibiotics has met with limited success and is still a big concern during post-surgery. Use of silver as an antibiotic treatment to prevent surgical infections is being explored due to the well-established antimicrobial properties of silver. However, in most cases silver is used in particulate form with wound dressings or with short-term devices such as catheters but not with load-bearing implants. We hypothesize that strongly adherent silver to load-bearing implants can offer longer-term solution towards infection in vivo. Keeping that in mind, the focus of this study was to understand the long-term release of silver ions, for a period of minimum 6months, from silver coated surface modified porous titanium implants.

Keywords: Additive manufacturing; Infection control; Load-bearing implants; Osteomyelitis; Silver.

Figure 1

A schematic showing fabrication steps of silver coated surface modified Ti implants and its simultaneous infection control ability as well as enhanced osseointegrative properties for load-bearing implants.

Figure 2

SEM images of (a) porous Ti surface, (b) nanotubes with silver deposition and (c) with nanotubes and silver deposition at a higher magnification.

Figure 3

SEM images of samples with silver deposition with loading rate 1 (Figures 2(a–c)) and loading rate 2 (Figures 2(d–f)).

Figure 4

Cumulative release profiles of silver ions from all samples in PBS medium at the end of 27 weeks using silver loading rate 1 with inset graphs showing continuous release of silver ions at latter time points. (Error bar values are very low and hence not properly visible for all time points although they are there for all time points; n=3)

Figure 5

Cumulative release profiles of silver ions from all samples in PBS medium at the end of 27 weeks using silver loading rate 2 with inset graphs showing continuous release of silver ions at latter time points. (Error bar values are very low and hence not properly visible for all time points although they are there for all time points; n=3)

Figure 6

Cumulative release profiles of silver ions from all samples in acetate buffer medium at the end of 4 weeks using silver loading rate 1. (Error bar values are very low and hence not properly visible for all time points; n=3).

Figure 7

Cumulative release profiles of silver ions from all samples in acetate buffer medium at the end of 4 weeks using silver loading rate 2. (Error bar values are very low and hence not properly visible for all time points; n=3).

Figure 8

SEM images of the surfaces of the samples showing the presence of silver particles after the end of 27 weeks in PBS medium.

Figure 9

SEM images of the surfaces of the samples showing the presence of silver particles after the end of 4 weeks in acetate buffer medium.

Figure 10

Photomicrographs showing the histological analysis after 12 weeks where signs of osteoid like new bone formation could be seen in orange/ red color. Modified Masson Goldner’s trichrome staining method was used.

Figure 11

SEM images of stained samples after 12 weeks showing the interfacial bonding between the implant and the bone tissue.