Alginate Hydrogels for In Vivo Bone Regeneration: The Immune Competence of the Animal Model Matters
Alginate Hydrogels for In Vivo Bone Regeneration: The Immune Competence of the Animal Model Matters
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DOI：
10.1089/ten.tea.2019.0310
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发表时间：
2020-03-10
影响因子：
4.1
通讯作者：
Cipitria, Amaia
中科院分区：
文献类型：
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作者：
Garske, Daniela S.;Schmidt-Bleek, Katharina;Cipitria, Amaia
具有可调生物物理性质的生物材料在组织工程方面具有巨大的潜力。获得性免疫系统在骨再生中起着重要作用。我们的目标是研究细胞负载藻酸盐水凝胶的再生潜力，这取决于动物模型的免疫状态。具体地说，研究了大鼠间充质基质细胞(MSC)负载、形成空洞的藻酸盐水凝胶的再生潜力，该水凝胶具有为成骨分化优化的硬度，在T细胞缺陷的Athymic Rowett(RNU)大鼠和免疫功能正常的SpragueDawley大鼠中，研究了5 mm临界大小的股骨缺损区的再生潜力。裸鼠RNU术后6周骨体积分数、骨密度、组织密度均较高。此外，这些动物缺损处的细胞总数和非淋巴细胞形态的细胞数量明显较多，而淋巴细胞样形态的细胞数量较少。水凝胶的降解速度较慢，剩余的藻酸盐碎片被较厚的纤维状胶囊包围。来源于藻酸盐残留物的骨化岛提示包裹的MSCs分化为成骨细胞并启动矿化过程。然而，这一效应不足以完全桥接两种动物模型中的骨缺损。藻酸盐水凝胶可用于运送MSCs，从而通过旁分泌信号招募内源性细胞，但需要额外的成骨刺激来再生临界大小的股骨节段性缺损。Impact声明：细胞缺陷的无细胞RNU裸鼠通常用于评估生物材料与人源性细胞结合的再生潜力。在这项研究中，我们显示了负载间充质基质细胞(MSC)的藻酸盐水凝胶对骨再生的影响取决于动物模型的免疫状态。此外，尽管藻酸盐水凝胶是研究可调节的生物物理特性对细胞反应和体内再生的影响的有趣材料，但它们与大鼠骨髓间充质干细胞的结合不足以完全桥接临界大小的股骨节段性缺损。为此，额外的成骨刺激，如生长因子输送是必要的。
Biomaterials with tunable biophysical properties hold great potential for tissue engineering. The adaptive immune system plays an important role in bone regeneration. Our goal is to investigate the regeneration potential of cell-laden alginate hydrogels depending on the immune status of the animal model. Specifically, the regeneration potential of rat mesenchymal stromal cell (MSC)-laden, void-forming alginate hydrogels, with a stiffness optimized for osteogenic differentiation, is studied in 5-mm critical-sized femoral defects, in both T cell-deficient athymic Rowett Nude (RNU) rats and immunocompetent Sprague Dawley rats. Bone volume fraction, bone mineral density, and tissue mineral density are higher for athymic RNU nude rats 6 weeks postsurgery. In addition, these animals show a significantly higher number of total cells and cells with non-lymphocyte morphology at the defect site, while the number of cells with lymphocyte-like morphology is lower. Hydrogel degradation is slower and the remaining alginate fragments are surrounded by a thicker fibrous capsule. Ossification islands originating from alginate residues suggest that encapsulated MSCs differentiate into the osteogenic lineage and initiate the mineralization process. However, this effect is insufficient to fully bridge the bone defect in both animal models. Alginate hydrogels can be used to deliver MSCs and thereby recruit endogenous cells through paracrine signaling, but additional osteogenic stimuli are needed to regenerate critical-sized segmental femoral defects.Impact statementT cell-deficient athymic RNU nude rats are commonly used to evaluate the regeneration potential of biomaterials in combination with cells of human origin. In this study, we show that the effect of mesenchymal stromal cell (MSC)-laden alginate hydrogels on bone regeneration differs depending of the immune status of the animal model. Furthermore, while alginate hydrogels are interesting materials to investigate the effect tunable biophysical properties on cell response and in vivo regeneration, their use in combination with rat MSCs is insufficient to fully bridge critical-sized segmental femoral defects. For this purpose, additional osteogenic stimuli such as growth factor delivery are necessary.