Caldon Jayson Esdaille

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.

Significance: This paper presents the synthetic artificial stem cell (SASC) system: a versatile therapy which provides the ability to tailor paracrine responses of different cells and provide a more potent regenerative effect for targeted tissues. Upon challenging the SASC system against an osteoarthritis model, we demonstrate that the factors combined tailored for chondrogenesis have a potent antiinflammatory and chondroprotective effect. This paper also demonstrates the in vivo capacity of SASC to attenuate proteoglycan depletion in the cartilage extracellular matrix while also improving biomechanical properties of the resulting cartilage. We report the first of many applications of the SASC system, which provides a promising step toward clinical translation of a minimally immunogenic stem cell with many commercial advantages over its biological counterpart.

Regenerative engineering is defined as the convergence of the disciplines of advanced material science, stem cell science, physics, developmental biology and clinical translation for the regenerati...