title: Gelatin-based Hydrogel Degradation and Tissue Interactionin vivo: Insights from Multimodal Preclinical Imaging in Immunocompetent Nude Mice.
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 investigatedin vivo(MRI, optical imaging, PET) andex 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.
authors.affiliation: Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Radiopharmaceutical and Chemical Biology, Dresden, Germany;; Technische Universität Dresden, Department of Chemistry and Food Chemistry, Dresden, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Tondera
authors.affiliation: Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Radiopharmaceutical and Chemical Biology, Dresden, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Hauser
authors.affiliation: Institute of Biomaterial Science and Berlin-Brandenburg Centre for Regenerative Therapies, Helmholtz-Zentrum Geesthacht, Teltow, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Krüger-Genge
authors.affiliation: Institute of Biomaterial Science and Berlin-Brandenburg Centre for Regenerative Therapies, Helmholtz-Zentrum Geesthacht, Teltow, Germany;; Helmholtz Virtual Institute "Multifunctional Biomaterials for Medicine", Teltow and Berlin.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Jung
authors.affiliation: Institute of Biomaterial Science and Berlin-Brandenburg Centre for Regenerative Therapies, Helmholtz-Zentrum Geesthacht, Teltow, Germany;; Helmholtz Virtual Institute "Multifunctional Biomaterials for Medicine", Teltow and Berlin.
authors.forename: Axel T
authors.initials: AT
authors.lastname: Neffe
authors.affiliation: Institute of Biomaterial Science and Berlin-Brandenburg Centre for Regenerative Therapies, Helmholtz-Zentrum Geesthacht, Teltow, Germany;; Helmholtz Virtual Institute "Multifunctional Biomaterials for Medicine", Teltow and Berlin.
authors.forename: Andreas
authors.initials: A
authors.lastname: Lendlein
authors.affiliation: Freie Universität Berlin, Institute of Veterinary Pathology, Berlin, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Klopfleisch
authors.affiliation: Technische Universität Dresden, Department of Chemistry and Food Chemistry, Dresden, Germany;; Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Dresden, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Steinbach
authors.affiliation: Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Radiopharmaceutical and Chemical Biology, Dresden, Germany.
authors.forename: Christin
authors.initials: C
authors.lastname: Neuber
authors.affiliation: Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Radiopharmaceutical and Chemical Biology, Dresden, Germany;; Technische Universität Dresden, Department of Chemistry and Food Chemistry, Dresden, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Pietzsch
mesh_terms: D000818:Animals; D001345:Autoradiography; D005780:Gelatin / Q000378:metabolism*; D006651:Histocytochemistry; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008819:Mice, Nude; D061848:Optical Imaging; D049268:Positron-Emission Tomography; D059748:Proteolysis; D044967:Serum / Q000737:chemistry
chemical_list: D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D005780:Gelatin
keywords: Autoradiography ex vivo; Biomaterials; Computed tomography; Magnetic resonance imaging; Optical imaging; Positron emission tomography.