Division of Polymer Chemistry, Department of Chemistry-Ångstrom Laboratory, Uppsala University, Uppsala, Sweden.
Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
Carbohydr Polym. 2018 Oct 1;197:641-648. doi: 10.1016/j.carbpol.2018.06.028. Epub 2018 Jun 7.
Monitoring hydrogel degradation in real time using noninvasive imaging techniques is of great interest for designing a scaffold in tissue engineering. We report the preparation of gadolinium (Gd)-labeled and injectable hyaluronic acid (HA) hydrogels that can be visualized using T- and T-weighted magnetic resonance imaging (MRI). An HA derivative functionalized with thiol and hydrazide was labeled using a diethylenetriaminepentaacetate complex modified with "clickable" dithiopyridyl functionalities (degree of modification was 3.77% with respect to HA repeat units). The HA derivative modified with cross-linkable groups and Gd complex exhibited relaxivities r = 3.78 mMs and r = 56.3 mMs. A hydrazone hydrogel network was obtained by mixing Gd-labeled HA-hydrazide and HA-aldehyde derivatives. Enzymatic hydrogel degradation could be followed using MRI because the MR images showed great correlation with the hydrogel mass loss. Ex vivo MRI of injected Gd-labeled hydrogels demonstrated that they show a significant contrast difference (SNR = 456; SNR = 459) from the surrounding tissues. These results indicate that our Gd-labeled HA hydrogel has great potential as an injectable biocompatible hydrogel that can be used for longitudinal tracking in vivo using MRI.
实时监测水凝胶的降解对于组织工程中支架的设计具有重要意义。我们报告了镧系元素（Gd）标记的可注射透明质酸（HA）水凝胶的制备，可通过 T1 和 T2 加权磁共振成像（MRI）进行可视化。一种具有巯基和酰肼官能团的 HA 衍生物通过用“可点击”二硫吡啶官能团修饰的二亚乙基三胺五乙酸酯复合物进行标记（相对于 HA 重复单元的修饰度为 3.77%）。具有可交联基团和 Gd 配合物的 HA 衍生物表现出弛豫率 r = 3.78 mMs 和 r = 56.3 mMs。通过混合 Gd 标记的 HA-酰肼和 HA-醛衍生物，得到了腙水凝胶网络。可以通过 MRI 跟踪酶促水凝胶的降解，因为 MRI 图像与水凝胶质量损失具有很好的相关性。注射的 Gd 标记水凝胶的离体 MRI 表明，它们与周围组织之间具有显著的对比差异（SNR = 456；SNR = 459）。这些结果表明，我们的 Gd 标记的 HA 水凝胶具有很大的潜力，可作为一种可注射的生物相容性水凝胶，可用于 MRI 进行体内的纵向跟踪。
