Chondrogenically primed mesenchymal stem cell-seeded alginate hydrogels promote early bone formation in critically-sized defects
Chondrogenically primed mesenchymal stem cell-seeded alginate hydrogels promote early bone formation in critically-sized defects
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DOI：
10.1016/j.eurpolymj.2015.07.021
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发表时间：
2015-11-01
影响因子：
6
通讯作者：
Kelly, D. J.
中科院分区：
文献类型：
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作者：
Cunniffe, G. M.;Vinardell, T.;Kelly, D. J.
使用骨髓间充质干细胞(MSCs)可以在体外构建肥大的软骨移植物。当这些工程化组织被植入体内时，它们被证明通过重述软骨内成骨的发育过程来诱导骨形成。藻酸盐是一种天然来源的生物相容性水凝胶，提供了一个诱人的3D环境来促进MSCs的体外软骨形成。此外，这种藻酸盐水凝胶有可能被用于工程规模的软骨组织，以促进大型骨缺损的软骨内骨再生。本研究的目的是研究软骨细胞负载的藻酸盐水凝胶在两种截然不同的临界大小的缺损模型中诱导愈合的能力。将骨髓来源的MSCs种植到藻酸盐水凝胶中，在含有转化生长因子-β3的情况下进行体外软骨诱导，然后将其植入大鼠颅骨或股骨的临界大小的缺损处。植入后4周的MU CT分析显示，与未处理的空白对照组相比，植入MSC的藻酸盐水凝胶治疗的股骨缺损处的矿化水平显著增加，在颅骨缺损处也观察到类似的结果。然而，任何新沉积的骨都是与藻酸盐材料相适应的，并且只发生在表面或藻酸盐被发现降解的地方。藻酸盐材料被发现在植入后8周在两个原位位置持续存在，其缓慢的降解速度似乎阻止了完全的骨再生。综上所述，尽管软骨源性MSC-藻酸盐构建物可以作为模板来治疗由膜内或软骨内成骨形成的骨骼中的临界大小的缺损，但需要进一步优化水凝胶本身的降解动力学，以加速骨组织沉积并促进此类缺损的完全再生。(C)2015爱思唯尔有限公司。保留所有权利。
Hypertrophic cartilaginous grafts can be engineered in vitro using bone marrow derived Mesenchymal Stem Cells (MSCs). When such engineered tissues are implanted in vivo they have been shown to induce bone formation by recapitulating aspects of the developmental process of endochondral ossification. Alginate, a naturally sourced and biocompatible hydrogel, offers an attractive 3D environment to facilitate the in vitro chondrogenesis of MSCs. Furthermore, such alginate hydrogels can potentially be used to engineer cartilage tissues of scale to promote endochondral bone regeneration in large bone defects. The aim of this study was to investigate the ability of chondrogenically-primed MSC-laden alginate hydrogels to induce healing in two distinct critically-sized defect models. Bone marrow derived MSCs were seeded into alginate hydrogels, chondrogenically primed in vitro in the presence of TGF-beta 3 and then implanted into either a critically-sized rat cranial or femoral defect. mu CT analysis 4 weeks post-implantation revealed significantly higher levels of mineralization within the femoral defects treated with MSC-laden alginate hydrogels compared to untreated empty controls, with similar results observed within the cranial defects. However, any newly deposited bone was generated appositional to the alginate material, and occurred only superficially or where the alginate was seen to degrade. Alginate material was found to persist within both orthotopic locations 8 weeks post-implantation, with its slow rate of degradation appearing to prevent complete bone regeneration. In conclusion, while chondrogenically primed MSC-alginate constructs can act as templates to treat critically-sized defects within bones formed through either intramembranous or endochondral ossification, further optimization of the degradation kinetics of the hydrogel itself will be required to accelerate bone tissue deposition and facilitate complete regeneration of such defects. (C) 2015 Elsevier Ltd. All rights reserved.