MRI Characterization of Gadolinium-Labelled Hyaluronic Acid (HA-(Gd-DTPA)) Uptake and Retention in Pericardium Tissue

Abstract

Approximately 1 million new patients are diagnosed with Temporomandibular joint (TMJ) disorders every year, 8% of which require total joint replacement (TJR). Due to the constant motion of joints, many of these implants fail due to wear and particulate release, requiring subsequent removal and revision. Hyaluronic acid (HA) has been utilized for some time as a therapeutic agent; the injectable version is used to treat various TMJ disorders and is routinely used after TMJ replacement to provide local lubrication. We explored the possibility of a HA-retaining biomaterial that can be incorporated into biomedical devices that will provide information regarding HA’s uptake and retention in pericardium tissue. Pericardium tissue, which has shown favorable interactions with HA, is used as a reference material to demonstrate HA retention capabilities and determine its possible use as a cushioning agent in biomedical devices. Using MR imaging, non-invasive imaging studies of HA-infused pericardium provides several advantages: (1) confirmation of HA concentration for mechanical stress studies and (2) tracking of in vivo injection location and release and degradation. Our lab was successful at labeling both 50k molecular weight (MW) and 1M MW HA with chelated gadolinium (GD-DTPA), with recovery rates of 50 and 83%, respectively. Results showed an ability of pericardium to substantially uptake HA-(Gd-DTPA) at high and low molecular weights (HMW, LMW) characterized by increase of T1 rates ranging from 4.4 to 11.09 s -1 at 250 and 500 µM concentrations of gadolinium. As a result, pericardium experienced a signal-to-noise ratio increase of 83.61% and 151.77% for low and high molecular weight HA-(Gd-DTPA), respectively, post incubation. After initial uptake, HMW HA-(Gd-DTPA) retained within pericardium at higher concentrations characterized by T1 rates 4.04 and 2.87 times greater than LMW over time. Pericardium incubated with high molecular weight HA-(Gd-DTPA) exhibited no measurable decrease in HA retention after initial wash for up to 1 week post incubation. HMW HA-(Gd-DTPA) reduced the tissue’s coefficient of friction by 77% and 80% at concentrations of 250 and 500 µM, respectively, providing adequate lubrication. In addition to the creation of a long term lubricating delivery system, characterizing the uptake and retention of HA at various molecular weights may improve the duration of action of intra-articular HA treatment, reduce the number of injections needed and subsequently, reduce costs of therapy.