• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>European Cells & Materials >Streamlined bioreactor-based production of human cartilage tissues
【24h】

Streamlined bioreactor-based production of human cartilage tissues

机译：简化的基于生物反应器的软骨组织生产

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Engineered tissue grafts have been manufactured using methods based predominantly on traditional labour-intensive manual benchtop techniques. These methods impart significant regulatory and economic challenges, hindering the successful translation of engineered tissue products to the clinic. Alternatively, bioreactor-based production systems have the potential to overcome such limitations. In this work, we present an innovative manufacturing approach to engineer cartilage tissue within a single bioreactor system, starting from freshly isolated human primary chondrocytes, through the generation of cartilaginous tissue grafts. The limited number of primary chondrocytes that can be isolated from a small clinically-sized cartilage biopsy could be seeded and extensively expanded directly within a 3D scaffold in our perfusion bioreactor (5.4  ± 0.9 doublings in 2 weeks), bypassing conventional 2D expansion in flasks. Chondrocytes expanded in 3D scaffolds better maintained a chondrogenic phenotype than chondrocytes expanded on plastic flasks (collagen type II mRNA, 18-fold; Sox-9, 11-fold). After this “3D expansion” phase, bioreactor culture conditions were changed to subsequently support chondrogenic differentiation for two weeks. Engineered tissues based on 3D-expanded chondrocytes were more cartilaginous than tissues generated from chondrocytes previously expanded in flasks. We then demonstrated that this streamlined bioreactor-based process could be adapted to effectively generate up-scaled cartilage grafts in a size with clinical relevance (50 mm diameter). Streamlined and robust tissue engineering processes, as the one described here, may be key for the future manufacturing of grafts for clinical applications, as they facilitate the establishment of compact and closed bioreactor-based production systems, with minimal automation requirements, lower operating costs, and increased compliance to regulatory guidelines.
机译：使用主要基于传统劳动密集型手动台式技术的方法制造了工程组织移植物。这些方法带来重大的监管和经济挑战，从而阻碍了工程纸巾产品成功应用于临床。或者，基于生物反应器的生产系统具有克服此类限制的潜力。在这项工作中，我们提出了一种创新的制造方法，可以在单个生物反应器系统中对软骨组织进行工程改造，从新鲜分离的人原代软骨细胞开始，直至生成软骨组织移植物。可以从临床规模小的软骨活检中分离出的有限数量的原代软骨细胞可以播种并直接在我们的灌注生物反应器的3D支架内广泛扩展（在2周内增加5.4±0.9倍），而绕过了烧瓶中常规的2D扩展。与在塑料瓶中扩增的软骨细胞相比，在3D支架中扩增的软骨细胞更好地保持了软骨形成的表型（II型胶原mRNA，18倍; Sox-9，11倍）。在“ 3D扩展”阶段之后，更改了生物反应器的培养条件，以随后支持软骨形成分化两周。基于3D扩增软骨细胞的工程组织比以前在烧瓶中扩增的软骨细胞产生的组织软骨性更高。然后我们证明了这种简化的基于生物反应器的过程可以适应于有效产生具有临床相关性（直径50毫米）的规模的大型软骨移植物。如此处所述，精简而强大的组织工程流程可能是未来制造临床应用移植物的关键，因为它们有助于建立紧凑且封闭的基于生物反应器的生产系统，同时自动化要求最低，运营成本较低，并增加了对监管准则的遵守。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号