Kino-Oka Masahiro, Maeda Yoshikatsu, Yamamoto Takeyuki, Sugawara Katsura, Taya Masahito
Division of Chemical Engineering, Graduate School of Engineering Science, Osaka University, 1-3 Machikaneyama, Toyonaka, Osaka 560-8531, Japan.
J Biosci Bioeng. 2005 Mar;99(3):197-207. doi: 10.1263/jbb.99.197.
For repairing articular cartilage defects, innovative techniques based on tissue engineering have been developed and are now entering into the practical stage of clinical application by means of grafting in vitro cultured products. A variety of natural and artificial materials available for scaffolds, which permit chondrocyte cells to aggregate, have been designed for their ability to promote cell growth and differentiation. From the viewpoint of the manufacturing process for tissue-engineered cartilage, the diverse nature of raw materials (seeding cells) and end products (cultured cartilage) oblige us to design a tailor-made process with less reproducibility, which is an obstacle to establishing a production doctrine based on bioengineering knowledge concerning growth kinetics and modeling as well as designs of bioreactors and culture operations for certification of high product quality. In this article, we review the recent advances in the manufacturing of tissue-engineered cartilage. After outlining the manufacturing processes for tissue-engineered cartilage in the first section, the second and third sections, respectively, describe the three-dimensional culture of chondrocytes with Aterocollagen gel and kinetic model consideration as a tool for evaluating this culture process. In the final section, culture strategy is discussed in terms of the combined processes of monolayer growth (ex vivo chondrocyte cell expansion) and three-dimensional growth (construction of cultured cartilage in the gel).
为修复关节软骨缺损,基于组织工程学的创新技术已被开发出来,目前正通过移植体外培养产物进入临床应用的实际阶段。已设计出多种可用于支架的天然和人工材料,这些材料能使软骨细胞聚集,并因其促进细胞生长和分化的能力而被选用。从组织工程软骨的制造过程来看,原材料(接种细胞)和最终产品(培养软骨)的多样性迫使我们设计一种定制化流程,但其可重复性较低,这成为基于有关生长动力学和建模的生物工程知识以及生物反应器设计和培养操作来建立确保高产品质量认证的生产原则的障碍。在本文中,我们综述了组织工程软骨制造方面的最新进展。在第一节概述组织工程软骨的制造过程后,第二和第三节分别描述了用阿特罗胶原蛋白凝胶进行软骨细胞的三维培养以及将动力学模型作为评估该培养过程的工具。在最后一节,从单层生长(体外软骨细胞扩增)和三维生长(在凝胶中构建培养软骨)的联合过程方面讨论了培养策略。