Hydraulic permeability and compressive properties of porcine and human synovium.

The synovium is a multilayer connective tissue separating the intra-articular spaces of the diarthrodial joint from the extra-synovial vascular and lymphatic supply. Synovium regulates drug transport into and out of the joint, yet its material properties remain poorly characterized. Here, we measured the compressive properties (aggregate modulus, Young's modulus, and Poisson's ratio) and hydraulic permeability of synovium with a combined experimental-computational approach. A compressive aggregate modulus and Young's modulus for the solid phase of synovium were quantified from linear regression of the equilibrium confined and unconfined compressive stress upon strain, respectively (HA = 4.3 ± 2.0 kPa, Es = 2.1 ± 0.75, porcine; HA = 3.1 ± 2.0 kPa, Es = 2.8 ± 1.7, human). Poisson's ratio was estimated to be 0.39 and 0.40 for porcine and human tissue, respectively, from moduli values in a Monte Carlo simulation. To calculate hydraulic permeability, a biphasic finite element model's predictions were numerically matched to experimental data for the time-varying ramp and hold phase of a single increment of applied strain (k = 7.4 ± 4.1 × 10-15 m4/N.s, porcine; k = 7.4 ± 4.3 × 10-15 m4/N.s, human). We can use these newly measured properties to predict fluid flow gradients across the tissue in response to previously reported intra-articular pressures. These values for material constants are to our knowledge the first available measurements in synovium that are necessary to better understand drug transport in both healthy and pathological joints.

Size-Dependent Effective Diffusivity in Healthy Human and Porcine Joint Synovium.

Intra-articular drug delivery can be effective in targeting a diseased joint but is hampered by rapid clearance times from the diarthrodial joint. The synovium is a multi-layered tissue that surrounds the diarthrodial joint and governs molecular transport into and out of the joint. No models of drug clearance through synovium exist to quantify diffusivity across solutes, tissue type and disease pathology. We previously have developed a finite element model of synovium as a porous, permeable, fluid-filled tissue and used an inverse method to determine urea's effective diffusivity (Deff) in de-vitalized synovium explants.22 Here we apply this method to determine Deff from unsteady diffusive transport of model solutes and confirm the role of molecular weight in solute transport. As molecular weight increased, Deff decreased in both human and porcine tissues, with similar behavior across the two species. Unsteady transport was well-described by a single exponential transient decay in concentration, yielding solute half-lives (t1/2) that compared favorably with the Deff determined from the finite element model fit. Determined values for Deff parallel prior observations of size-dependent in vivo drug clearance and provide an intrinsic parameter with greater ability to resolve size-dependence in vitro. Thus, this work forms the basis for understanding the influence of size on drug transport in synovium and can guide future studies to elucidate the role of charge and tissue pathology on the transport of therapeutics in healthy and pathological human synovium.