Theranostics 2019; 9(15):4255-4264. doi:10.7150/thno.35606 This issue

Research Paper

Dual-Channel Fluorescence Imaging of Hydrogel Degradation and Tissue Regeneration in the Brain

G. Kate Park1,2, Su-Hwan Kim3, Kyungmin Kim3, Priyanka Das2, Byung-Gee Kim1,3,4, Satoshi Kashiwagi2, Hak Soo Choi2✉, Nathaniel S. Hwang1,3,4✉

1. Interdisciplinary Program in Bioengineering, Seoul National University, Seoul 151-742, South Korea
2. Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
3. School of Chemical and Biological Engineering, Institute of Chemical Processes, Seoul National University, Seoul 151-742, South Korea
4. Institute of Bioengineering, BioMAX Institute, Institute of Molecular Biology and Genetics, Seoul National University, Seoul 151-742, South Korea

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license ( See for full terms and conditions.
Park GK, Kim SH, Kim K, Das P, Kim BG, Kashiwagi S, Choi HS, Hwang NS. Dual-Channel Fluorescence Imaging of Hydrogel Degradation and Tissue Regeneration in the Brain. Theranostics 2019; 9(15):4255-4264. doi:10.7150/thno.35606. Available from

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Graphic abstract

The ability of brain tissue to regenerate is limited; therefore, brain diseases (i.e., trauma, stroke, tumors) often lead to irreversible motor and cognitive impairments. Therapeutic interventions using various types of injectable biomaterials have been investigated to promote endogenous neural differentiation. Despite promising results in pre-clinical studies, the translation of regenerative medicine to the clinic has many challenges due to the lack of reliable imaging systems to achieve accurate evaluation of the treatment efficacy.

Methods: In this study, we developed a dual-channel fluorescence imaging technique to simultaneously monitor tissue ingrowth and scaffold disintegration. Enzymatically crosslinked gelatin-hyaluronic acid hydrogel was labeled with 800 nm fluorophore, ZW800-3a, while the regenerated tissue was highlighted with 700 nm brain-specific contrast agent, Ox1.

Results: Using the multichannel fluorescence imaging system, tissue growth and degradation of the NIR hydrogel were simultaneously imaged in the brain of mice. Images were further analyzed and reconstructed to show both visual and quantitative information of each stage of a therapeutic period.

Conclusion: Dual-channel in vivo imaging systems can provide highly accurate visual and quantitative information of the brain tissue ingrowth for the evaluation of the therapeutic effect of NIR hydrogel through a simple and fast operating procedure.

Keywords: NIR injectable hydrogel, Brain tissue regeneration, Multichannel imaging, Fluorescence imaging