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Photocrosslinked Dextran-Based Hydrogels as Carrier System for the Cells and Cytokines Induce Bone Regeneration in Critical Size Defects in Mice

机译：光交联的基于葡聚糖的水凝胶作为细胞和细胞因子的载体系统诱导小鼠关键尺寸缺陷的骨再生。

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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.
机译：多年来，改性生物材料一直是建立新型骨替代品的研究重点。在我们之前采用不同细胞培养物的体外研究中，我们开发了基于光可交联葡聚糖衍生物的化学和机械特性的水凝胶，并证明了它们的细胞相容性及其对成骨细胞和内皮细胞增殖的有益作用。在目前的体内研究中，我们研究了小鼠关键尺寸缺陷中基于光交联葡聚糖的水凝胶，以评估其作为细胞或特定血管生成增强细胞因子诱导骨形成的载体系统的潜力。我们可以证明，通过优化的实验室实践，可以将水凝胶的内毒素含量降低至低于美国食品药品管理局（FDA）的限值。基于葡聚糖的水凝胶装有内皮细胞的单培养物或人成骨细胞与内皮细胞的共培养物或基质衍生的生长因子（SDF-1）。将支架植入小鼠临界大小的颅骨缺损中，并通过μCt分析，组织学和免疫组织学评估其对骨骼形成的影响。我们的研究表明，通过SDF-1或内皮细胞的单培养促进血管新生可在生理水平上诱导骨再生。这些体内结果表明，基于葡聚糖的水凝胶复合物在骨再生中具有将细胞和细胞因子递送至缺损部位的潜力。

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