In Vivo Imaging of Composite Hydrogel Scaffold Degradation Using CEST MRI and Two-Color NIR Imaging

Wei Zhu; Chengyan Chu; Shreyas Kuddannaya; Yue Yuan; Piotr Walczak; Anirudha Singh; Xiaolei Song; Jeff W M Bulte

doi:10.1002/adfm.201903753

In Vivo Imaging of Composite Hydrogel Scaffold Degradation Using CEST MRI and Two-Color NIR Imaging

Adv Funct Mater. 2019 Sep 5;29(36):1903753. doi: 10.1002/adfm.201903753. Epub 2019 Jul 8.

Authors

Wei Zhu^{1

2}, Chengyan Chu^{1

2}, Shreyas Kuddannaya^{1

2}, Yue Yuan^{1

2}, Piotr Walczak^{1

2}, Anirudha Singh^{3

4}, Xiaolei Song^{1

2}, Jeff W M Bulte^{1

2

4

5

6}

Affiliations

¹ Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, the Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
² Cellular Imaging Section, Institute for Cell Engineering, the Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
³ Department of Urology, the James Buchanan Brady Urological Institute, the Johns Hopkins University School of Medicine, Baltimore, MD, 21287.
⁴ Department of Chemical & Biomolecular Engineering, the Johns Hopkins University Whiting School of Engineering, Baltimore, MD, 21218.
⁵ Department of Biomedical Engineering, the Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
⁶ Department of Oncology, the Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.

Abstract

Hydrogel scaffolding of stem cells is a promising strategy to overcome initial cell loss and manipulate cell function post-transplantation. Matrix degradation is a requirement for downstream cell differentiation and functional tissue integration, which determines therapeutic outcome. Therefore, monitoring of hydrogel degradation is essential for scaffolded cell replacement therapies. We show here that chemical exchange saturation transfer magnetic resonance imaging (CEST MRI) can be used as a label-free imaging platform for monitoring the degradation of crosslinked hydrogels containing gelatin (Gel) and hyaluronic acid (HA), of which the stiffness can be fine-tuned by varying the ratio of the Gel:HA. By labeling Gel and HA with two different NIR dyes having distinct emission excitation frequencies, we show here that the HA signal remains stable for 42 days, while the Gel signal gradually decreases to <25% of its initial value at this time point. Both imaging modalities were in excellent agreement for both the time course and relative value of CEST MRI and NIR signals (R²=0.94). These findings support the further use of CEST MRI for monitoring biodegradation and optimizing of gelatin-containing hydrogels in a label-free manner.

Keywords: CEST MRI; NIR imaging; biodegradation; gelatin; hyaluronic acid; hydrogel.

Abstract

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