Enhanced nutrient transport improves the depth-dependent properties of tri-layered engineered cartilage constructs with zonal co-culture of chondrocytes and MSCs
Enhanced nutrient transport improves the depth-dependent properties of tri-layered engineered cartilage constructs with zonal co-culture of chondrocytes and MSCs
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DOI：
10.1016/j.actbio.2017.06.025
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发表时间：
2017-08-01
影响因子：
9.7
通讯作者：
Mauck, Robert L.
中科院分区：
文献类型：
--
作者：
Kim, Minwook;Farrell, Megan J.;Mauck, Robert L.
由于天然组织的复杂性，软骨组织工程的仿生设计是一个挑战。虽然许多研究已经产生了具有接近天然本体性质的结构，但再现天然组织的深度依赖性特征仍然是一个挑战。此外，工程化构建体中营养转运和基质积累的限制阻碍了大型构建体的中心核心内的成熟。为了克服这些局限性，我们制作了三层结构，其使用与MSC共培养的区域来源的软骨细胞来概括天然组织的深度依赖性细胞组织和功能特性。我们还引入了多孔中空纤维（HFs）和HFs/棉线来增强营养物质的运输。我们的研究结果表明，三层结构与深度依赖的组织和性能可以制造。HF或HF/线程的添加改善了中央核心区域中的基质积累。对于HF/螺纹，三层结构深部的局部模量几乎与天然组织相匹配，尽管中心区域的性能仍然较低。这些结构再现了原生组织的带状组织和深度依赖性，并证明了逐层制造方案有望仿生修复局灶性软骨defects.Statement of significance关节软骨是一种高度组织化的组织，由细胞、细胞外基质蛋白和原纤维方向的带状异质性驱动，导致深度依赖性的机械性能。因此，在组织工程构建体中再现天然软骨的功能特性需要这样的形态组织的仿生设计，这在软骨组织工程中仍然是一个挑战。这项研究表明，逐层制造方案，包括区域特异性关节CH和MSC的共培养，可以再现天然软骨的深度依赖性特征和机械性能，同时最大限度地减少对大量软骨细胞的需求。此外，引入多孔中空纤维（与棉线组合）增强了三层结构的营养输送和深度依赖性。这种三层结构可以为局部软骨修复提供关键优势。这些构建体有望恢复天然组织结构和功能，并且在与相邻宿主组织的区域间整合以及在植入后提供更适当的应变转移方面可能是有益的。(C)2017 Acta Materialia Inc.由爱思唯尔有限公司出版。保留所有权利。
Biomimetic design in cartilage tissue engineering is a challenge given the complexity of the native tissue. While numerous studies have generated constructs with near-native bulk properties, recapitulating the depth-dependent features of native tissue remains a challenge. Furthermore, limitations in nutrient transport and matrix accumulation in engineered constructs hinders maturation within the central core of large constructs. To overcome these limitations, we fabricated tri-layered constructs that recapitulate the depth-dependent cellular organization and functional properties of native tissue using zonally derived chondrocytes co-cultured with MSCs. We also introduced porous hollow fibers (HFs) and HFs/cotton threads to enhance nutrient transport. Our results showed that tri-layered constructs with depth-dependent organization and properties could be fabricated. The addition of HFs or HFs/threads improved matrix accumulation in the central core region. With HF/threads, the local modulus in the deep region of tri-layered constructs nearly matched that of native tissue, though the properties in the central regions remained lower. These constructs reproduced the zonal organization and depth-dependent properties of native tissue, and demonstrate that a layer-by-layer fabrication scheme holds promise for the biomimetic repair of focal cartilage defects.Statement of significanceArticular cartilage is a highly organized tissue driven by zonal heterogeneity of cells, extracellular matrix proteins and fibril orientations, resulting in depth-dependent mechanical properties. Therefore, the recapitulation of the functional properties of native cartilage in a tissue engineered construct requires such a biomimetic design of the morphological organization, and this has remained a challenge in cartilage tissue engineering. This study demonstrates that a layer-by-layer fabrication scheme, including co-cultures of zone-specific articular CHs and MSCs, can reproduce the depth-dependent characteristics and mechanical properties of native cartilage while minimizing the need for large numbers of chondrocytes. In addition, introduction of a porous hollow fiber (combined with a cotton thread) enhanced nutrient transport and depth-dependent properties of the tri-layered construct. Such a tri-layered construct may provide critical advantages for focal cartilage repair. These constructs hold promise for restoring native tissue structure and function, and may be beneficial in terms of zone-to-zone integration with adjacent host tissue and providing more appropriate strain transfer after implantation. (C) 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.