Acute and Subacute ToxicityIn Vivoof Thermal-Sprayed Silver Containing Hydroxyapatite Coating in Rat Tibia

Abstract

To reduce the incidence of implant-associated infection, we previously developed a novel coating technology using hydroxyapatite (HA) containing silver (Ag). This study examined in vivo acute and subacute toxicity associated with the Ag-HA coating in rat tibiae. Ten-week-old rats received implantation of HA-, 2% Ag-HA-, or 50% Ag-HA-coated titanium rods. Concentrations of silver in serum, brain, liver, kidneys, and spleen were measured in the acute phase (2–4 days after treatment) and subacute phase (4–12 weeks after treatment). Biochemical and histological examinations of those organs were also performed. Mean serum silver concentration peaked in the acute phase and then gradually decreased. Mean silver concentrations in all examined organs from the 2% Ag-HA coating groups showed no significant differences compared with the HA coating group. No significant differences in mean levels of glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, lactate dehydrogenase, creatinine, or blood urea nitrogen were seen between the three groups and controls. Histological examinations of all organs revealed no abnormal pathologic findings. No acute or subacute toxicity was seen in vivo for 2% Ag-HA coating or HA coating. Ag-HA coatings on implants may represent biologically safe antibacterial biomaterials and may be of value for reducing surgical-site infections related to implantation.

Silver oxide‐containing hydroxyapatite coating supports osteoblast function and enhances implant anchorage strength in rat femur

“…The entire amount of silver is unlikely to exert systemic toxicity, because silver in the coating material is slowly released and rapidly eliminated from the body. Tsukamoto et al have reported that Ag–HA coating shows neither acute nor subacute toxicity in rats. Therefore, 3% Ag–HA may be regarded as a safe implant processing material for use in humans.…”

Atomic Layer Deposition of a Silver Nanolayer on Advanced Titanium Orthopedic Implants Inhibits Bacterial Colonization and Supports Vascularized de Novo Bone Ingrowth

“…This means that ALD can give truly atomic scale control of the deposition process and can produce ultrathin films with excellent uniformity and conformity, even on complex high aspect ratio 3D structures . The coating we describe in this study is so thin that the total quantity of active material is kept to a minimum (below levels of detection by ICP‐MS in our study), which helps to reduce concern relating to systemic toxicity of nanolayer silver‐coated orthopedic implants …”

“…The majority of studies examining the antimicrobial potential of silver for dental/orthopedic applications rely on dissolution of Ag particles from either cements or surface coatings for titanium. These studies generally report a >2 log‐fold increase in microbicidal activity, although silver particles are highly mobile and potentially toxic, with their tissue accumulation characteristics being largely unexplored . Investigation of silver‐nanoparticle films that are bonded to titanium is therefore of great interest as a method for reduction of postsurgical osteolytic infections, while preventing the release of potentially toxic quantities of silver.…”

“…The majority of approaches for dissolution of Ag + or Cu ions for antimicrobial applications is directed toward localized release via gradual solubilization. Although localized release of Ag‐nanoparticles via dissolution achieves excellent antimicrobial effects in vitro and in vivo, this approach is associated with increased silver levels in both serum and systemic organs in addition to evidence of toxicity.…”

Silver-Containing Hydroxyapatite Coating Reduces Biofilm Formation by Methicillin-ResistantStaphylococcus aureusIn Vitro and In Vivo

“…Tsukamoto et al previously demonstrated that, in a rat tibia model with Ag-HA-coated implants, serum silver levels were sufficiently low to avoid harmful effects, and no degeneration was observed in the brain, liver, kidneys, or spleen. The amount of silver required for Ag-HA coating of femoral replacements in humans is low enough to avoid argyria [34]. In fact, in a 1-year follow-up study, we found that none of the patients developed any adverse reactions to silver from Ag-HA-coated implants in total hip arthroplasties [35].…”