Effect of molecular weight and tissue layer on solute partitioning in the knee meniscus

Knee meniscus tissue is partly vascularized, meaning that nutrients must be transported through the extracellular matrix of the avascular portion to reach resident cells. Similarly, drugs used as therapeutic agents to treat meniscal pathologies rely on transport through the tissue. The driving force of diffusive transport is the gradient of concentration, which depends on molecular solubility. The meniscus is organized into a core region sandwiched between the tibial and femoral superficial layers. Structural differences exist across meniscal regions; therefore, regional differences in solubility are also hypothesized.

Samples from the core, tibial and femoral layers were obtained from 5 medial and 5 lateral porcine menisci. The partition coefficient (K) of fluorescein, 3 ​kDa and 40 ​kDa dextrans in the layers of the meniscus was measured using an equilibration experiment. The effect of meniscal compartment, layer, and solute molecular weight on K was analyzed using a three-way ANOVA.

K ranged from a high of ∼2.9 in fluorescein to a low of ∼0.1 in 40 ​kDa dextran and was inversely related to the solute molecular weight across all tissue regions. Tissue layer only had a significant effect on partitioning of 40k Dex solute, which was lower in the tibial surface layer relative to the core (p ​= ​0.032).

This study provides insight into depth-dependent partitioning in the meniscus, indicating the limiting effect of the meniscus superficial layer on solubility increases with solute molecular size. This illustrates how the surface layers could potentially reduce the effectiveness of drug delivery therapies incorporating large molecules (>40 ​kDa).