Morejon Andy, Schwartz Gabi, Best Thomas M, Travascio Francesco, Jackson Alicia R
Department of Mechanical and Aerospace Engineering, University of Miami, Coral Gables, FL, USA.
Department of Biomedical Engineering, University of Miami, Coral Gables, FL, USA.
Osteoarthr Cartil Open. 2023 Apr 8;5(2):100360. doi: 10.1016/j.ocarto.2023.100360. eCollection 2023 Jun.
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 () 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 was analyzed using a three-way ANOVA.
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).
膝关节半月板组织部分血管化，这意味着营养物质必须通过无血管部分的细胞外基质运输才能到达驻留细胞。同样，用于治疗半月板病变的治疗药物也依赖于在组织中的运输。扩散运输的驱动力是浓度梯度，其取决于分子溶解度。半月板被组织成夹在胫骨和股骨表层之间的核心区域。半月板各区域存在结构差异；因此，也推测存在溶解度的区域差异。
从5个内侧和5个外侧猪半月板获取核心层、胫骨层和股骨层的样本。使用平衡实验测量荧光素、3 kDa和40 kDa葡聚糖在半月板各层中的分配系数（）。使用三因素方差分析分析半月板隔室、层和溶质分子量对的影响。
范围从荧光素中的约2.9到40 kDa葡聚糖中的约0.1，并且在所有组织区域中与溶质分子量呈负相关。组织层仅对40k Dex溶质的分配有显著影响，胫骨表层相对于核心层的分配较低（p = 0.032）。
本研究深入了解了半月板中深度依赖性分配，表明半月板表层对溶解度的限制作用随溶质分子大小增加。这说明了表层如何可能降低包含大分子（>40 kDa）的药物递送疗法的有效性。
