(352g) An Injectable Hyaluronic Acid-Based Nano-Contrast Agent for CT Detection of Inflammation and Osteoarthritis

Osteoarthritis (OA) is a common and painful chronic joint disease that affects large joints such as the knees, spine, hips, and shoulders. It is the most prevalent chronic joint disease in the world, with half of the world’s population aged 65 or older suffering from some form. OA relates to the decomposition of hyaluronic acid (HA) in the joints, a high molecular weight non-sulfated poly(glycosaminoglycan) and the main component of synovial fluid, a viscous (physical) hydrogel that lubricates the joint surfaces and reduces friction between articular cartilages with movement. Current diagnosis involves imaging with MRI or X-rays. An FDA-approved treatment includes HA injections in the knee of OA patients (~2 mL of HA once a week; for 3-5 weeks), providing pain relief for up to 6 months, and is recommended when patients cannot control pain with analgesic drugs or tolerate those drugs. We develop a minimally-invasive, diagnostic HA-based nano-contrast agent that can be administered intra-articularly in the knee of OA animals and retained, similar to FDA-approved HA, and can provide a more sensitive detection of OA / joint injuries by X-ray CT (computed tomography). The injectable nano-scaffold can hinder bone friction, similarly to viscosupplemented HA, and simultaneously quantify joint degradation and inflammation through X-rays. The utilized method takes advantage of reactive oxygen species (ROS) produced in inflamed joints. The presence of those in conjunction with our nano-scaffold leads to X-ray CT signal enhancement. Among our achievements is the low amount of metal (<1 mg) that is utilized, and the use of photon-counting spectral CT (PCD-CT). Synthesis and characterization of the material will be shown, in vitro studies with ROS and signal enhancement, as well as results from our first in vivo studies.