Hyaluronic acid–British anti-Lewisite as a safer chelation therapy for the treatment of arthroplasty-related metallosis

Abstract

Cobalt-containing alloys are useful for orthopedic applications due to their low volumetric wear rates, corrosion resistance, high mechanical strength, hardness, and fatigue resistance. Unfortunately, these prosthetics release significant levels of cobalt ions, which was only discovered after their widespread implantation into patients requiring hip replacements. These cobalt ions can result in local toxic effects—including peri-implant toxicity, aseptic loosening, and pseudotumor—as well as systemic toxic effects—including neurological, cardiovascular, and endocrine disorders. Failing metal-on-metal (MoM) implants usually necessitate painful, risky, and costly revision surgeries. To treat metallosis arising from failing MoM implants, a synovial fluid-mimicking chelator was designed to remove these metal ions. Hyaluronic acid (HA), the major chemical component of synovial fluid, was functionalized with British anti-Lewisite (BAL) to create a chelator (BAL-HA). BAL-HA effectively binds cobalt and rescues in vitro cell vitality (up to 370% of cells exposed to IC 50 levels of cobalt) and enhances the rate of clearance of cobalt in vivo ( t 1/2 from 48 h to 6 h). A metallosis model was also created to investigate our therapy. Results demonstrate that BAL-HA chelator system is biocompatible and capable of capturing significant amounts of cobalt ions from the hip joint within 30 min, with no risk of kidney failure. This chelation therapy has the potential to mitigate cobalt toxicity from failing MoM implants through noninvasive injections into the joint.

Investigating the association between blood cobalt and gallstones: a cross-sectional study utilizing NHANES data

“…Notably, older individuals aged ≥60 years exhibited heightened susceptibility to cobalt exposure compared to those under 60 years old. This observation may be attributed to the increased likelihood of older individuals utilizing medically derived cobalt-alloyed prostheses such as hip and knee implants ( 14 , 31 , 32 ). Obesity serves as a predisposing factor for gallstone formation, while estrogen enhances the risk by promoting hepatic cholesterol synthesis and secretion while inhibiting bile salt synthesis.…”

“…In the field of medical prosthesis implantation, cobalt-containing alloys are widely utilized due to their exceptional properties such as wear resistance, corrosion resistance, high mechanical strength, hardness, and fatigue resistance. However, these alloys also pose a risk for endogenous cobalt exposure ( 14 ).…”

Extreme Serum Titanium Concentration Induced by Acetabular Cup Failure: Unveiling a Unique Scenario of Titanium Alloy Debris Accumulation

“…Despite titanium being considered less toxic than cobalt, our case highlights the potential for adverse tissue reactions in the absence of CoCr alloy components. Unfortunately, no titanium-chelating agents, comparable to those recently developed for cobalt, are currently available [ 33 ].…”