Endochondral bone formation in gelatin methacrylamide hydrogel with embedded cartilage-derived matrix particles

Endochondral bone formation in gelatin methacrylamide hydrogel with embedded cartilage-derived matrix particles
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DOI:
10.1016/j.biomaterials.2014.10.020
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发表时间:
2015-01-01
期刊:
影响因子:
14
通讯作者:
Malda, Jos
Malda, Jos
中科院分区:
工程技术1区
文献类型:
--
作者:
Visser, Jetze;Gawlitta, Debby;Malda, Jos

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软骨内成骨的自然过程是骨组织工程研究的热点之一。然而,为了产生相关尺寸的骨移植物,需要细胞载体,其确保高扩散速率并促进基质形成,通过其降解来平衡。因此,我们开始在明胶甲基丙烯酰胺(GelMA)水凝胶中设计软骨内骨,并嵌入多能基质细胞(MSC)和软骨衍生基质(CDM)颗粒。发现CDM颗粒可以刺激体外GelMA水凝胶中MSC形成软骨模板。在皮下大鼠模型中,该模板随后被重塑为矿化骨组织,包括骨髓腔。在此过程中,GelMA几乎完全降解。含或不含CDM颗粒的GelMA的钙化程度无显著差异:分别为42.5 ± 2.5%和39.5 ± 8.3%(平均值±标准差)。有趣的是,在骨软骨组织中,一半结构中软骨细胞的存在完全阻碍了另一半结构中MSC的骨形成。这项工作提供了一个新的途径工程相关大小的骨移植物,形成软骨内骨内的可降解水凝胶。(C)2014爱思唯尔有限公司版权所有。
The natural process of endochondral bone formation in the growing skeletal system is increasingly inspiring the field of bone tissue engineering. However, in order to create relevant-size bone grafts, a cell carrier is required that ensures a high diffusion rate and facilitates matrix formation, balanced by its degradation. Therefore, we set out to engineer endochondral bone in gelatin methacrylamide (GelMA) hydrogels with embedded multipotent stromal cells (MSCs) and cartilage-derived matrix (CDM) particles. CDM particles were found to stimulate the formation of a cartilage template by MSCs in the GelMA hydrogel in vitro. In a subcutaneous rat model, this template was subsequently remodeled into mineralized bone tissue, including bone-marrow cavities. The GelMA was almost fully degraded during this process. There was no significant difference in the degree of calcification in GelMA with or without CDM particles: 42.5 +/- 2.5% vs. 39.5 +/- 8.3% (mean +/- standard deviation), respectively. Interestingly, in an osteochondral setting, the presence of chondrocytes in one half of the constructs fully impeded bone formation in the other half by MSCs. This work offers a new avenue for the engineering of relevant-size bone grafts, by the formation of endochondral bone within a degradable hydrogel. (C) 2014 Elsevier Ltd. All rights reserved.