Weber Patrick, Maier Annalena, Fercher David, Asadikorayem Maryam, Zenobi-Wong Marcy
Tissue Engineering + Biofabrication Laboratory, Department of Health Sciences and Technology, ETH Zürich, Otto-Stern-Weg 7, 8093, Zürich, Switzerland.
Mater Today Bio. 2024 Oct 26;29:101302. doi: 10.1016/j.mtbio.2024.101302. eCollection 2024 Dec.
Accurately assessing cartilage tissue degradation is a big challenge in osteoarthritis (OA) research, as histology only provides information about a 2D tissue section, and currently available contrast agents for tomographic evaluation suffer from low specificity. In this study, we present a modular platform based on zwitterionic carboxybetaine (CBAA) to create multivalent polymeric contrast agents for x-ray computed tomography (CT) with high specificity towards the anionic glycosaminoglycans in the cartilage tissue. By copolymerizing CBAA with different ratios of anionic and cationic iodinated comonomers, we created a library of polymers with net charges ranging from strongly anionic to strongly cationic. The polymers were applied onto osteochondral plugs with different degradation states and the resulting CT images compared to histological stainings. In healthy tissues, the bulk contrast enhancement was strongly correlated with polymer charge, with cationic polymers reaching a 2-fold stronger contrast compared to established small molecule contrast agents. While a further increase in cationic charge slowed the penetration, it increased the polymer's specificity, thereby enabling the most cationic polymer C40 (40 mol% cationic iodinated comonomer) to discriminate accurately between tissues treated with IL-1β for 0, 1, 2 and 3 weeks. Moreover, this polymer also showed a strong local specificity, visualizing local differences in GAG distribution with significantly increased accuracy compared to the controls. Our polymer contrast agents show the importance of multivalency and charge control for the accurate, volumetric detection of GAGs in the cartilage tissue and paves the way towards new contrast agents in- and outside of the clinic.
准确评估软骨组织降解是骨关节炎（OA）研究中的一项重大挑战，因为组织学仅提供有关二维组织切片的信息，并且目前用于断层扫描评估的造影剂特异性较低。在本研究中，我们提出了一种基于两性离子羧基甜菜碱（CBAA）的模块化平台，以创建用于X射线计算机断层扫描（CT）的多价聚合物造影剂，该造影剂对软骨组织中的阴离子糖胺聚糖具有高特异性。通过将CBAA与不同比例的阴离子和阳离子碘化共聚单体共聚，我们创建了一系列净电荷范围从强阴离子到强阳离子的聚合物。将这些聚合物应用于具有不同降解状态的骨软骨栓，并将所得的CT图像与组织学染色进行比较。在健康组织中，整体对比增强与聚合物电荷密切相关，与已有的小分子造影剂相比，阳离子聚合物的对比度增强了两倍。虽然阳离子电荷的进一步增加会减缓渗透，但它提高了聚合物的特异性，从而使最阳离子化的聚合物C40（40摩尔%阳离子碘化共聚单体）能够准确区分用IL-1β处理0、1、2和3周的组织。此外，这种聚合物还表现出很强的局部特异性，与对照相比，以显著提高的准确性可视化了GAG分布的局部差异。我们的聚合物造影剂显示了多价性和电荷控制对于软骨组织中GAG的准确、体积检测的重要性，并为临床内外的新型造影剂铺平了道路。
