| Autor: |
Ude CC; The Cato T. Laurencin Institute for Regenerative Engineering, University of Connecticut, Farmington, CT 06030.; Department of Orthopaedic Surgery, University of Connecticut Health, Farmington, CT 06030., Schmidt SJ; Department of Chemistry, Carnegie Mellon University, Pittsburgh, PA 15213., Laurencin S; The Cato T. Laurencin Institute for Regenerative Engineering, University of Connecticut, Farmington, CT 06030.; Department of Orthopaedic Surgery, University of Connecticut Health, Farmington, CT 06030., Shah S; The Cato T. Laurencin Institute for Regenerative Engineering, University of Connecticut, Farmington, CT 06030.; Department of Orthopaedic Surgery, University of Connecticut Health, Farmington, CT 06030.; Department of Chemical and Biomolecular Engineering, University of Connecticut, Storrs, CT 06269., Esdaille J; The Cato T. Laurencin Institute for Regenerative Engineering, University of Connecticut, Farmington, CT 06030.; Department of Orthopaedic Surgery, University of Connecticut Health, Farmington, CT 06030., Kan HM; The Cato T. Laurencin Institute for Regenerative Engineering, University of Connecticut, Farmington, CT 06030.; Department of Orthopaedic Surgery, University of Connecticut Health, Farmington, CT 06030., Holt BD; Department of Chemistry, Carnegie Mellon University, Pittsburgh, PA 15213., Arnold AM; Department of Chemistry, Carnegie Mellon University, Pittsburgh, PA 15213., Wolf ME; Department of Chemistry, Carnegie Mellon University, Pittsburgh, PA 15213., Nair LS; The Cato T. Laurencin Institute for Regenerative Engineering, University of Connecticut, Farmington, CT 06030.; Department of Orthopaedic Surgery, University of Connecticut Health, Farmington, CT 06030.; Department of Chemical and Biomolecular Engineering, University of Connecticut, Storrs, CT 06269.; Department of Biomedical Engineering, University of Connecticut, Storrs, CT 06269.; Department of Materials Science and Engineering, University of Connecticut, Storrs, CT 06269.; Institute of Materials Science, University of Connecticut, Storrs, CT 06269., Sydlik SA; Department of Chemistry, Carnegie Mellon University, Pittsburgh, PA 15213.; Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213., Laurencin CT; The Cato T. Laurencin Institute for Regenerative Engineering, University of Connecticut, Farmington, CT 06030.; Department of Orthopaedic Surgery, University of Connecticut Health, Farmington, CT 06030.; Department of Chemical and Biomolecular Engineering, University of Connecticut, Storrs, CT 06269.; Department of Biomedical Engineering, University of Connecticut, Storrs, CT 06269.; Department of Materials Science and Engineering, University of Connecticut, Storrs, CT 06269.; Institute of Materials Science, University of Connecticut, Storrs, CT 06269.; Department of Craniofacial Sciences, School of Dental Medicine, University of Connecticut Health, Farmington, CT 06030. |
| Abstrakt: |
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. |
