title: Biocompatibility and inflammatory response in vitro and in vivo to gelatin-based biomaterials with tailorable elastic properties.
abstract: Hydrogels prepared from gelatin and lysine diisocyanate ethyl ester provide tailorable elastic properties and degradation behavior. Their interaction with human aortic endothelial cells (HAEC) as well as human macrophages (Mɸ) and granulocytes (Gɸ) were explored. The experiments revealed a good biocompatibility, appropriate cell adhesion, and cell infiltration. Direct contact to hydrogels, but not contact to hydrolytic or enzymatic hydrogel degradation products, resulted in enhanced cyclooxygenase-2 (COX-2) expression in all cell types, indicating a weak inflammatory activation in vitro. Only Mɸ altered their cytokine secretion profile after direct hydrogel contact, indicating a comparably pronounced inflammatory activation. On the other hand, in HAEC the expression of tight junction proteins, as well as cytokine and matrix metalloproteinase secretion were not influenced by the hydrogels, suggesting a maintained endothelial cell function. This was in line with the finding that in HAEC increased thrombomodulin synthesis but no thrombomodulin membrane shedding occurred. First in vivo data obtained after subcutaneous implantation of the materials in immunocompetent mice revealed good integration of implants in the surrounding tissue, no progredient fibrous capsule formation, and no inflammatory tissue reaction in vivo. Overall, the study demonstrates the potential of gelatin-based hydrogels for temporal replacement and functional regeneration of damaged soft 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: Sandra
authors.initials: S
authors.lastname: Ullm
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
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: 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, Germany.
authors.forename: Tim P
authors.initials: TP
authors.lastname: Gebauer
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, Germany.
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, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Lendlein
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, Germany.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Jung
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. Electronic address: j.pietzsch@hzdr.de.
authors.forename: Jens
authors.initials: J
authors.lastname: Pietzsch
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000009:adverse effects / Q000737:chemistry* / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000032:analysis / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D004548:Elasticity; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D005260:Female; D005780:Gelatin / Q000009:adverse effects / Q000737:chemistry* / Q000276:immunology; D006801:Humans; D020100:Hydrogels / Q000009:adverse effects / Q000737:chemistry / Q000378:metabolism; D007249:Inflammation / Q000209:etiology* / Q000276:immunology; D008239:Lysine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008422:Materials Testing; D051379:Mice; D019736:Prostheses and Implants / Q000009:adverse effects*
chemical_list: D001672:Biocompatible Materials; D016207:Cytokines; D020100:Hydrogels; D005780:Gelatin; D051546:Cyclooxygenase 2; D008239:Lysine
keywords: Cyclooxygenases; Cytokines; Endothelial cells; Macrophages; Matrix metalloproteinases; Thrombomodulin