Theranostics 2016; 6(12):2114-2128. doi:10.7150/thno.16614

Research Paper

Gelatin-based Hydrogel Degradation and Tissue Interaction in vivo: Insights from Multimodal Preclinical Imaging in Immunocompetent Nude Mice

Christoph Tondera1,2, Sandra Hauser1, Anne Krüger-Genge3, Friedrich Jung3,4, Axel T. Neffe3,4, Andreas Lendlein3,4, Robert Klopfleisch5, Jörg Steinbach2,6, Christin Neuber1, Jens Pietzsch1,2 ✉

1. Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Radiopharmaceutical and Chemical Biology, Dresden, Germany;
2. Technische Universität Dresden, Department of Chemistry and Food Chemistry, Dresden, Germany;
3. Institute of Biomaterial Science and Berlin-Brandenburg Centre for Regenerative Therapies, Helmholtz-Zentrum Geesthacht, Teltow, Germany;
4. Helmholtz Virtual Institute “Multifunctional Biomaterials for Medicine”, Teltow and Berlin;
5. Freie Universität Berlin, Institute of Veterinary Pathology, Berlin, Germany;
6. Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Dresden, Germany.

Abstract

Hydrogels based on gelatin have evolved as promising multifunctional biomaterials. Gelatin is crosslinked with lysine diisocyanate ethyl ester (LDI) and the molar ratio of gelatin and LDI in the starting material mixture determines elastic properties of the resulting hydrogel. In order to investigate the clinical potential of these biopolymers, hydrogels with different ratios of gelatin and diisocyanate (3-fold (G10_LNCO3) and 8-fold (G10_LNCO8) molar excess of isocyanate groups) were subcutaneously implanted in mice (uni- or bilateral implantation). Degradation and biomaterial-tissue-interaction were investigated in vivo (MRI, optical imaging, PET) and ex vivo (autoradiography, histology, serum analysis). Multimodal imaging revealed that the number of covalent net points correlates well with degradation time, which allows for targeted modification of hydrogels based on properties of the tissue to be replaced. Importantly, the degradation time was also dependent on the number of implants per animal. Despite local mechanisms of tissue remodeling no adverse tissue responses could be observed neither locally nor systemically. Finally, this preclinical investigation in immunocompetent mice clearly demonstrated a complete restoration of the original healthy tissue.

Keywords: Autoradiography ex vivo, Biomaterials, Computed tomography, Magnetic resonance imaging, Optical imaging, Positron emission tomography.

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How to cite this article:
Tondera C, Hauser S, Krüger-Genge A, Jung F, Neffe AT, Lendlein A, Klopfleisch R, Steinbach J, Neuber C, Pietzsch J. Gelatin-based Hydrogel Degradation and Tissue Interaction in vivo: Insights from Multimodal Preclinical Imaging in Immunocompetent Nude Mice. Theranostics 2016; 6(12):2114-2128. doi:10.7150/thno.16614. Available from http://www.thno.org/v06p2114.htm