Engineering of hyaline cartilage with a calcified zone using bone marrow stromal cells

Engineering of hyaline cartilage with a calcified zone using bone marrow stromal cells
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DOI:
10.1016/j.joca.2015.04.010
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发表时间:
2015-08-01
影响因子:
7
通讯作者:
Kandel, R. A.
Kandel, R. A.
中科院分区:
医学2区
文献类型:
--
作者:
Lee, W. D.;Hurtig, M. B.;Kandel, R. A.

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目的:在健康关节中,钙化软骨区(ZCC)提供关节软骨和软骨下骨之间的机械结合。对这一结构特征的概括应该有助于抵抗关节运动产生的恒定剪切力,并防止组织工程软骨的分层。以前在软骨-基质界面创建ZCC的方法依赖于策略性地使用外源支架和粘合剂,这些支架和粘合剂容易因降解和磨损而失效。相反,我们报道了一种成功的ZCC无支架工程,利用绵羊骨髓基质细胞(BMSCs)作为两个软骨带的细胞来源,将组织工程化软骨与多孔可生物降解骨替代物整合在一起。设计:将BMSCs预分化为软骨细胞,收获后在含三碘甲腺原氨酸(T3)的多孔聚磷酸钙基质上生长。结果:该方法形成了两个不同的区域:透明软骨和邻近基质的钙化软骨,前者积累了蛋白多糖和II型胶原,后者额外积累了矿物质和X型胶原。与未钙化的对照相比,具有钙化界面的构建物具有与天然绵羊骨软骨组织相当的压缩强度和更高的界面剪切强度。结论:该方法通过引入钙化区,改进了现有的无支架软骨组织工程方法。由于该方案不使用异种材料,它将适合用于临床前的大型动物研究。(C)2015年国际骨性关节炎研究会。爱思唯尔有限公司出版。保留所有权利。
Objective: In healthy joints, a zone of calcified cartilage (ZCC) provides the mechanical integration between articular cartilage and subchondral bone. Recapitulation of this architectural feature should serve to resist the constant shear force from the movement of the joint and prevent the delamination of tissue-engineered cartilage. Previous approaches to create the ZCC at the cartilage-substrate interface have relied on strategic use of exogenous scaffolds and adhesives, which are susceptible to failure by degradation and wear. In contrast, we report a successful scaffold-free engineering of ZCC to integrate tissue-engineered cartilage and a porous biodegradable bone substitute, using sheep bone marrow stromal cells (BMSCs) as the cell source for both cartilaginous zones.Design: BMSCs were predifferentiated to chondrocytes, harvested and then grown on a porous calcium polyphosphate substrate in the presence of triiodothyronine (T3). T3 was withdrawn, and additional predifferentiated chondrocytes were placed on top of the construct and grown for 21 days.Results: This protocol yielded two distinct zones: hyaline cartilage that accumulated proteoglycans and collagen type II, and calcified cartilage adjacent to the substrate that additionally accumulated mineral and collagen type X. Constructs with the calcified interface hadcomparable compressive strength to native sheep osteochondral tissue and higher interfacial shear strength compared to control without a calcified zone.Conclusion: This protocol improves on the existing scaffold-free approaches to cartilage tissue engineering by incorporating a calcified zone. Since this protocol employs no xenogeneic material, it will be appropriate for use in preclinical large-animal studies. (C) 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.