Dorsey Shauna M, Haris Mohammad, Singh Anup, Witschey Walter R T, Rodell Christopher B, Kogan Feliks, Reddy Ravinder, Burdick Jason A
Department of Bioengineering, University of Pennsylvania, 240 Skirkanich Hall, 210 South 33rd Street, Philadelphia, Pennsylvania 19104, United States.
Department of Radiology, University of Pennsylvania, 422 Curie Boulevard, Philadelphia, Pennsylvania 19104, United States.
ACS Biomater Sci Eng. 2015 Apr 13;1(4):227-237. doi: 10.1021/ab500097d. Epub 2015 Mar 25.
Injectable biomaterials are being developed for a wide range of biomedical applications; however, characterization of materials (e.g., distribution, chemical composition) after injection is often difficult and relies on invasive and destructive procedures. To address this problem, this study utilizes a new magnetic resonance imaging (MRI) acquisition technique based on chemical exchange saturation transfer (CEST), where the signal relies on the exchange of protons in specific molecules with bulk water protons. Such a signal can be generated from specific functional groups endogenous to or engineered into a desired material. Here, CEST MRI was used to visualize injectable hyaluronic acid (HA) hydrogels either alone or after injection into tissue. The CEST effect was shown to track with changes in material properties-as hydrogel macromer concentration was increased, the CEST contrast increased linearly. Furthermore, CEST MRI was used to detect hydrogels injected into cardiac explants with an increase in signal at the hydrogel site relative to the surrounding myocardial signal. Unlike conventional MRI, CEST can simultaneously visualize and discriminate between different injectable materials based on their unique chemistry. To illustrate this, we tuned the CEST signal to detect differences in two hydrogel systems based on their dominant functional groups. The covalent addition of an arginine-based peptide to HA hydrogels led to a 2-fold increase in signal when the exchangeable amine (-NH) protons in the peptide were targeted. Thus, CEST MRI could become a valuable tool for studying injectable hydrogel properties and enable further optimization of biomaterial therapies aimed at clinical translation.
可注射生物材料正被开发用于广泛的生物医学应用；然而，注射后材料的表征（如分布、化学成分）往往很困难，且依赖于侵入性和破坏性程序。为了解决这个问题，本研究采用了一种基于化学交换饱和转移（CEST）的新型磁共振成像（MRI）采集技术，其中信号依赖于特定分子中的质子与大量水质子的交换。这样的信号可以由目标材料内源性或设计引入的特定官能团产生。在这里，CEST MRI被用于可视化单独的可注射透明质酸（HA）水凝胶或注射到组织后的水凝胶。结果表明，CEST效应随材料性质的变化而变化——随着水凝胶大分子单体浓度的增加，CEST对比度呈线性增加。此外，CEST MRI被用于检测注射到心脏外植体中的水凝胶，水凝胶部位的信号相对于周围心肌信号增加。与传统MRI不同，CEST可以根据不同可注射材料独特的化学性质同时对其进行可视化和区分。为了说明这一点，我们调整了CEST信号以检测基于其主要官能团的两种水凝胶系统之间的差异。当靶向肽中可交换的胺（-NH）质子时，将基于精氨酸的肽共价添加到HA水凝胶中会导致信号增加两倍。因此，CEST MRI可能成为研究可注射水凝胶性质的有价值工具，并有助于进一步优化旨在临床转化的生物材料疗法。
