Liang Yajie, Bar-Shir Amnon, Song Xiaolei, Gilad Assaf A, Walczak Piotr, Bulte Jeff W M
Russell H. Morgan Dept. of Radiology and Radiological Science, Division of MR Research, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Russell H. Morgan Dept. of Radiology and Radiological Science, Division of MR Research, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Dept. of Chemical & Biomolecular Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Dept. of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Dept. of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Biomaterials. 2015 Feb;42:144-50. doi: 10.1016/j.biomaterials.2014.11.050. Epub 2014 Dec 16.
Composite hyaluronic acid (HA) hydrogels containing gelatin are used in regenerative medicine as tissue-mimicking scaffolds for improving stem cell survival. Once implanted, it is assumed that these biomaterials disintegrate over time, but at present there is no non-invasive imaging technique available with which such degradation can be directly monitored in vivo. We show here the potential of chemical exchange saturation transfer magnetic resonance imaging (CEST MRI) as a label-free non-invasive imaging technique to monitor dynamic changes in scaffold composition in vivo. The CEST properties of the three individual hydrogel components (HA, GelinS, and polyethylene glycol diacrylate) were first measured in vitro. The complete hydrogel was then injected into the brain of immunodeficient rag2(-/-) mice and CEST MR images were obtained at day 1 and 7 post-transplantation. In vitro, GelinS gave the strongest CEST signal at 3.6 ppm offset from the water peak, originating from the amide protons present in gelatin. In vivo, a significant decrease in CEST signal was observed at 1 week post-implantation. These results were consistent with the biodegradation of the GelinS component, as validated by fluorescent microscopy of implanted hydrogels containing Alexa Fluor 488-labeled GelinS. Our label-free imaging approach should be useful for further development of hydrogel formulations with improved composition and stability.
含有明胶的复合透明质酸（HA）水凝胶在再生医学中用作模仿组织的支架，以提高干细胞存活率。一旦植入，人们认为这些生物材料会随着时间推移而分解，但目前尚无可用的非侵入性成像技术来在体内直接监测这种降解情况。我们在此展示了化学交换饱和转移磁共振成像（CEST MRI）作为一种无标记非侵入性成像技术在监测体内支架成分动态变化方面的潜力。首先在体外测量了三种单独水凝胶成分（HA、GelinS和聚乙二醇二丙烯酸酯）的CEST特性。然后将完整的水凝胶注射到免疫缺陷的rag2（-/-）小鼠大脑中，并在移植后第1天和第7天获得CEST MR图像。在体外，GelinS在相对于水峰偏移3.6 ppm处给出最强的CEST信号，该信号源自明胶中存在的酰胺质子。在体内，植入后1周观察到CEST信号显著降低。这些结果与GelinS成分的生物降解一致，含有Alexa Fluor 488标记的GelinS的植入水凝胶的荧光显微镜检查验证了这一点。我们的无标记成像方法对于进一步开发具有改进成分和稳定性的水凝胶制剂应该是有用的。
