Long-term stable fibrin gels for cartilage engineering

Long-term stable fibrin gels for cartilage engineering
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DOI:
10.1016/j.biomaterials.2006.08.027
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发表时间:
2007-01-01
期刊:
影响因子:
14
通讯作者:
Blunk, Torsten
Blunk, Torsten
中科院分区:
工程技术1区
文献类型:
--
作者:
Eyrich, Damela;Brandl, Ferdinand;Blunk, Torsten

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水凝胶支架系统保持长期的形状稳定性和机械完整性对于软骨组织工程的应用是至关重要的。在这项研究中,我们的目的是改善市售的纤维蛋白凝胶,以开发一种长期稳定的纤维蛋白凝胶,随后,研究了体外软骨工程的优化凝胶的适用性。只有最终纤维蛋白原浓度为25 mg/ml或更高、Ca2+浓度为20 mM和pH为6.8 - 9的纤维蛋白凝胶是透明的,并在实验持续时间内稳定三周。相比之下,当制备浓度超出这些范围的纤维蛋白凝胶时,获得的混浊凝胶在几周内收缩并完全溶解。在流变学表征实验中,优化的凝胶显示出宽的线性粘弹性区域,并承受高达10,000 Pa的机械载荷。悬浮在优化的纤维蛋白凝胶中的牛软骨细胞增殖良好,并产生细胞外基质(ECM)组分糖胺聚糖和11型胶原蛋白。当最初每个构建体(5mm,直径,2mm厚)接种3百万个细胞或更多时,培养5周后,获得了均匀分布在整个构建体中的连贯软骨ECM。所开发的纤维蛋白凝胶也被建议用于其他组织工程应用,其中长期稳定的水凝胶似乎是理想的。(c)2006爱思唯尔有限公司保留所有权利。
It is essential that hydrogel scaffold systems maintain long-term shape stability and mechanical integrity for applications in cartilage tissue engineering. Within this study, we aimed at the improvement of a commercially available fibrin gel in order to develop a long-term stable fibrin gel and, subsequently, investigated the suitability of the optimized gel for in vitro cartilage engineering. Only fibrin gels with a final fibrinogen concentration of 25 mg/ml or higher, a Ca2+ concentration of 20 mm and a pH between 6.8 and 9 were transparent and stable for three weeks, the duration of the experiment. In contrast, when preparing fibrin gels with concentrations out of these ranges, turbid gels were obtained that shrank and completely dissolved within a few weeks. In rheological characterization experiments, the optimized gels showed a broad linear viscoelastic region and withstood mechanical loadings of up to 10,000 Pa. Bovine chondrocytes suspended in the optimized fibrin gels proliferated well and produced the extracellular matrix (ECM) components glycosaminoglycans and collagen type 11. When initially seeding 3 million cells or more per construct (5 mm, diameter, 2 mm thick), after 5 weeks of culture, a coherent cartilaginous ECM was obtained that was homogenously distributed throughout the whole construct. The developed fibrin gels are suggested also for other tissue engineering applications in which long-term stable hydrogels appear desirable. (c) 2006 Elsevier Ltd. All rights reserved.