Injectable hyaluronic acid hydrogels with the capacity for magnetic resonance imaging

Injectable hyaluronic acid hydrogels with the capacity for magnetic resonance imaging
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DOI:
10.1016/j.carbpol.2018.06.028
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发表时间:
2018-10-01
影响因子:
11.2
通讯作者:
Hilborn, Jons
Hilborn, Jons
中科院分区:
化学1区
文献类型:
--
作者:
Bermejo-Velasco, Daniel;Dou, Weiqiang;Hilborn, Jons

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利用无创成像技术实时监测水凝胶降解对组织工程支架的设计具有重要意义。我们报道了钆(Gd)标记和可注射透明质酸(HA)水凝胶的制备,可以通过T-1和t -2加权磁共振成像(MRI)进行可视化。以巯基和肼为官能团的HA衍生物,用二乙烯三胺五乙酸酯配合物修饰“可点击”的二硫代吡啶基官能团(HA重复单元的修饰度为3.77%)进行标记。经交联基团和Gd配合物修饰的HA衍生物的松弛度r(1) = 3.78 mM(-1)s(-1)和r(2) = 56.3 mM(-1)s(-1)。将gd标记的ha -肼和ha -醛衍生物混合得到了一个腙水凝胶网络。由于核磁共振图像与水凝胶质量损失有很大的相关性,因此可以使用核磁共振跟踪酶解水凝胶的降解。注射的gd标记水凝胶的离体MRI显示其与周围组织的对比度有显著差异(sncoronal = 456; SNRaxial = 459)。这些结果表明,我们的gd标记的透明质酸水凝胶具有巨大的潜力,作为一种可注射的生物相容性水凝胶,可用于通过MRI进行体内纵向跟踪。
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-1- and T-2-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(1) = 3.78 mM(-1)s(-1) and r(2) = 56.3 mM(-1)s(-1). 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 (SNRcoronal = 456; SNRaxial = 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.