Revell Christopher M, Reynolds Catherine E, Athanasiou Kyriacos A
Department of Bioengineering, Rice University, 6100 Main Street, Keck Hall, Suite 116, Houston, TX 77005, USA.
Ann Biomed Eng. 2008 Sep;36(9):1441-8. doi: 10.1007/s10439-008-9524-x. Epub 2008 Jun 24.
Current forays into tissue engineering of articular cartilage in vitro using the self-assembling method have produced constructs possessing significant extracellular matrix and resulting mechanical properties. However, large numbers of native articular chondrocytes are necessary to produce functional engineered cartilage; all previous work with the self-assembling process has used 5.5 x 10(6) cells/construct. In this study, the effects of initial cell seeding (0.25-11 x 10(6) cells/construct) on tissue quality were investigated. Results showed that tissue engineered articular cartilage was formed, when using at least 2 million cells/construct, possessing dimensional, compositional, and compressive properties approaching those of native tissue. It was noted that higher seeding contributed to thicker constructs with larger diameters and had a significant effect on resulting biochemical and biomechanical properties. It was further observed that aggregate modulus increased with increased seeding. By combining gross morphological, histological, biochemical, and biomechanical results, an optimal initial seeding for the self-assembling process of 3.75 x 10(6) cells/construct was identified. This finding enhances the translatability of this tissue engineering process by reducing the number of cells needed for tissue engineering of articular cartilage by 32% while maintaining essential tissue properties.
目前利用自组装方法在体外进行关节软骨组织工程的尝试已产生了具有大量细胞外基质和相应力学性能的构建体。然而,要生成功能性工程软骨需要大量天然关节软骨细胞;此前所有关于自组装过程的研究都使用了5.5×10⁶个细胞/构建体。在本研究中,研究了初始细胞接种量(0.25 - 11×10⁶个细胞/构建体)对组织质量的影响。结果表明,当每个构建体使用至少200万个细胞时,可形成组织工程化关节软骨,其尺寸、成分和压缩性能接近天然组织。值得注意的是,较高的接种量有助于形成直径更大、更厚的构建体,并对最终的生化和生物力学性能产生显著影响。进一步观察到,聚集模量随接种量增加而增加。综合大体形态学、组织学、生化和生物力学结果,确定了自组装过程的最佳初始接种量为3.75×10⁶个细胞/构建体。这一发现提高了该组织工程过程的可转化性,在保持基本组织特性的同时,将关节软骨组织工程所需的细胞数量减少了32%。