Photocrosslinked Dextran-Based Hydrogels as Carrier System for the Cells and Cytokines Induce Bone Regeneration in Critical Size Defects in Mice
Ulrike Ritz,
Marc Eberhardt,
Anja Klein,
Petra Frank,
Hermann Götz,
Alexander Hofmann,
Pol Maria Rommens,
Ulrich Jonas
Affiliations
Ulrike Ritz
Biomatics Group, Department of Orthopaedics and Traumatology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany
Marc Eberhardt
Biomatics Group, Department of Orthopaedics and Traumatology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany
Anja Klein
Biomatics Group, Department of Orthopaedics and Traumatology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany
Petra Frank
Macromolecular Chemistry, Department Chemistry Biology, University of Siegen, 57076 Siegen, Germany
Hermann Götz
Biomatics Group, Platform Biomaterials, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany
Alexander Hofmann
Biomatics Group, Department of Orthopaedics and Traumatology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany
Pol Maria Rommens
Biomatics Group, Department of Orthopaedics and Traumatology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany
Ulrich Jonas
Macromolecular Chemistry, Department Chemistry Biology, University of Siegen, 57076 Siegen, Germany
Modified biomaterials have for years been the focus of research into establishing new bone substitutes. In our preceding in vitro study employing different cell cultures, we developed chemically and mechanically characterized hydrogels based on photocrosslinkable dextran derivatives and demonstrated their cytocompatibility and their beneficial effects on the proliferation of osteoblasts and endothelial cells. In the present in vivo study, we investigate photocrosslinked dextran-based hydrogels in critical size defects in mice to evaluate their potential as carrier systems for cells or for a specific angiogenesis enhancing cytokine to induce bone formation. We could demonstrate that, with optimized laboratory practice, the endotoxin content of hydrogels could be reduced below the Food and Drug Administration (FDA)-limit. Dextran-based hydrogels were either loaded with a monoculture of endothelial cells or a co-culture of human osteoblasts with endothelial cells, or with stromal-derived-growth factor (SDF-1). Scaffolds were implanted into a calvarial defect of critical size in mice and their impact on bone formation was assessed by µCt-analyses, histology and immunohistology. Our study demonstrates that promotion of angiogenesis either by SDF-1 or a monoculture of endothelial cells induces bone regeneration at a physiological level. These in vivo results indicate the potential of dextran-based hydrogel composites in bone regeneration to deliver cells and cytokines to the defect site.
