Label-free imaging of gelatin-containing hydrogel scaffolds

Yajie Liang; Amnon Bar-Shir; Xiaolei Song; Assaf A Gilad; Piotr Walczak; Jeff W M Bulte

doi:10.1016/j.biomaterials.2014.11.050

Label-free imaging of gelatin-containing hydrogel scaffolds

Biomaterials. 2015 Feb:42:144-50. doi: 10.1016/j.biomaterials.2014.11.050. Epub 2014 Dec 16.

Authors

Yajie Liang¹, Amnon Bar-Shir¹, Xiaolei Song¹, Assaf A Gilad¹, Piotr Walczak¹, Jeff W M Bulte²

Affiliations

¹ 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.
² 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. Electronic address: jwmbulte@mri.jhu.edu.

Abstract

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.

Keywords: CEST MRI; Gelatin; Hyaluronic acid; Hydrogel; Scaffold; Transplantation.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Animals
Gelatin / pharmacology*
Hydrogel, Polyethylene Glycol Dimethacrylate / chemistry
Hydrogel, Polyethylene Glycol Dimethacrylate / pharmacology*
Imaging, Three-Dimensional*
Implants, Experimental
Magnetic Resonance Imaging
Male
Mice
Staining and Labeling*
Tissue Scaffolds / chemistry*

Substances

Hydrogel, Polyethylene Glycol Dimethacrylate
Gelatin

Abstract

Publication types

MeSH terms

Substances

Grants and funding