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,Ulrich Jonas,Alexander Hofmann,Petra Frank,Hermann Götz,Anja Klein,Pol Rommens

doi:10.3390/gels4030063

Abstract

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.

Highlights

Increasing knowledge about fracture healing has been gained in the last decades for bone defects of critical sizes, many mechanistic details of healing are still unknown
Dextran-based hydrogels as 3D scaffolds were prepared as described in the materials and methods section
We could demonstrate in these studies that human primary osteoblasts as well as endothelial cells both grow and proliferate on these dextran-based hydrogels [21]

Summary

Introduction

Increasing knowledge about fracture healing has been gained in the last decades for bone defects of critical sizes, many mechanistic details of healing are still unknown. These medical conditions represent a general challenge for surgeons and no agreement exists on an optimal therapeutic strategy. Autologous bone grafting is commonly performed, yet this method often inflicts donor graft morbidity with consequences such as pain, stress and surgical revision [1]. The volume of autologous bone graft that can be salvaged is tightly limited. Alternative approaches are either based on pharmacological methods, for example the administration of cytokines or growth factors in the bone defect, or they involve living cells (like cell-based tissue engineering) [2].

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