Composite chondroitin-6-sulfate/dermatan sulfate/chitosan scaffolds for cartilage tissue engineering
Composite chondroitin-6-sulfate/dermatan sulfate/chitosan scaffolds for cartilage tissue engineering
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DOI：
10.1016/j.biomaterials.2007.01.027
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发表时间：
2007-05-01
期刊：
影响因子：
14
通讯作者：
Hu, Yu-Chen
中科院分区：
文献类型：
--
作者：
Chen, Yen-Lin;Lee, Hsiao-Ping;Hu, Yu-Chen
将单种糖胺聚糖（GAG）如硫酸软骨素（CSC）偶联到壳聚糖上有利于软骨细胞培养和细胞外基质（ECM）的产生，但与其他次要GAG物质如硫酸皮肤聚糖（DS）偶联是否能进一步提高ECM的产生尚不清楚。本研究采用响应面法（Response Surface Methodology， RSM）设计了不同配方的CSC/DS/壳聚糖支架用于软骨工程，并研究了单个GAG物质在软骨形成中的作用。CSC/DS配方既不影响支架的物理性能，也不影响细胞粘附，但会影响细胞形态、GAGs和胶原蛋白的产生以及软骨细胞基因的表达。RSM分析所阐明的线性效应表明，在水平范围内，较高的CSC水平有利于GAGs和胶原蛋白的产生，而较低的DS水平有利于这些反应。然而，DS的二次效应以及CSC和DS之间的双向相互作用也有助于GAGs和胶原蛋白的产生。因此，根据RSM预测和实验验证，最佳配方为每个支架含有2.8 mg CSC和0.01 mg DS。本研究证实了DS在软骨组织工程中的重要性，并暗示了利用RSM设计合理的CSC/DS/壳聚糖支架的可行性。(c) 2007 Elsevier Ltd.版权所有。
Conjugating a single glycosaminoglycan (GAG) species such as chondroitin-6-sulfate (CSC) to chitosan is beneficial to chondrocyte culture and extracellular matrix (ECM) production, but whether fabrication of 3D chitosan scaffolds with additional minor GAG species such as dermatan sulfate (DS) further improves the ECM production is unknown. In this study, Response Surface Methodology (RSM) was employed to design CSC/DS/chitosan scaffolds of various formulations for cartilage engineering and to investigate the roles of individual GAG species in cartilage formation. The CSC/DS formulation affected neither the physical properties of scaffolds nor cell adhesion, but influenced cell morphology, GAGs and collagen production and chondrocytic gene expression. The linear effects elucidated by RSM analysis suggested that within the level range higher CSC levels favored GAGs and collagen production, whereas lower DS levels were desired for these responses. Nonetheless, the quadratic effects of DS and two-way interactions between CSC and DS also contributed to the GAGs and collagen production. Accordingly, the optimal formulation, as predicted by RSM and validated by experiments, comprised 2.8 mg CSC and 0.01 mg DS per scaffold. This study confirmed the importance of DS in cartilage tissue engineering and implicated the feasibility of rational CSC/DS/chitosan scaffold design with the aid of RSM. (c) 2007 Elsevier Ltd. All rights reserved.