DiDomenico Chris D, Goodearl Andrew, Yarilina Anna, Sun Victor, Mitra Soumya, Sterman Annette Schwartz, Bonassar Lawrence J
Meinig School of Biomedical Engineering, Cornell University, 145 Weill Hall, Ithaca, NY 14853 e-mail:
AbbVie Inc., 100 Research Drive, Worcester, MA 01605 e-mail:
J Biomech Eng. 2017 Sep 1;139(9). doi: 10.1115/1.4037202.
Because of the heterogeneous nature of articular cartilage tissue, penetration of potential therapeutic molecules for osteoarthritis (OA) through the articular surface (AS) is complex, with many factors that affect transport of these solutes within the tissue. Therefore, the goal of this study is to investigate how the size of antibody (Ab) variants, as well as application of cyclic mechanical loading, affects solute transport within healthy cartilage tissue. Penetration of fluorescently tagged solutes was quantified using confocal microscopy. For all the solutes tested, fluorescence curves were obtained through the articular surface. On average, diffusivities for the solutes of sizes 200 kDa, 150 kDa, 50 kDa, and 25 kDa were 3.3, 3.4, 5.1, and 6.0 μm2/s from 0 to 100 μm from the articular surface. Diffusivities went up to a maximum of 16.5, 18.5, 20.5, and 23.4 μm2/s for the 200 kDa, 150 kDa, 50 kDa, and 25 kDa molecules, respectively, from 225 to 325 μm from the surface. Overall, the effect of loading was very significant, with maximal transport enhancement for each solute ranging from 2.2 to 3.4-fold near 275 μm. Ultimately, solutes of this size do not diffuse uniformly nor are convected uniformly, through the depth of the cartilage tissue. This research potentially holds great clinical significance to discover ways of further optimizing transport into cartilage and leads to effective antibody-based treatments for OA.
由于关节软骨组织的异质性，用于骨关节炎（OA）的潜在治疗分子透过关节表面（AS）的过程很复杂，有许多因素会影响这些溶质在组织内的转运。因此，本研究的目的是调查抗体（Ab）变体的大小以及循环机械负荷的施加如何影响健康软骨组织内的溶质转运。使用共聚焦显微镜对荧光标记溶质的渗透进行定量。对于所有测试的溶质，通过关节表面获得荧光曲线。平均而言，大小为200 kDa、150 kDa、50 kDa和25 kDa的溶质在距关节表面0至100μm范围内的扩散系数分别为3.3、3.4、5.1和6.0μm²/s。对于200 kDa、150 kDa、50 kDa和25 kDa的分子，在距表面225至325μm范围内，扩散系数分别最高可达16.5、18.5、20.5和23.4μm²/s。总体而言，负荷的影响非常显著，每种溶质在距表面约275μm处的最大转运增强范围为2.2至3.4倍。最终，这种大小的溶质在软骨组织深度内既不会均匀扩散也不会均匀对流。这项研究对于发现进一步优化向软骨内转运的方法具有潜在的重大临床意义，并可能带来基于抗体的OA有效治疗方法。
