Functional tissue engineering of articular cartilage through dynamic loading of chondrocyte-seeded agarose gels
Functional tissue engineering of articular cartilage through dynamic loading of chondrocyte-seeded agarose gels
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DOI：
10.1115/1.429656
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发表时间：
2000-06-01
影响因子：
1.7
通讯作者：
Ateshian, GA
中科院分区：
文献类型：
--
作者：
Mauck, RL;Soltz, MA;Ateshian, GA
由于关节软骨无血管的特性，其再生和修复能力非常有限。尽管现有的许多组织工程软骨在模拟透明软骨的形态和生化外观方面取得了成功，但通常在力学性能上不如天然组织。在本研究中，我们验证了这样一个假设：在生理应变水平下施加动态变形载荷可促进细胞接种琼脂糖支架中的软骨细胞基质合成，从而产生比自由溶胀对照更具功能性的工程化组织构建体。使用定制设计的生物反应器对细胞接种的琼脂糖圆盘进行动态单轴压缩加载，峰 - 峰压缩应变幅度为10%，频率为1Hz，每天3次（加载1小时，休息1小时），每周5天，持续4周。结果表明，在加载28天后，动态加载的圆盘的平衡聚集模量比自由溶胀对照增加了6倍（100±16 kPa对15±8 kPa，p<0.001）。动态加载的圆盘还显示出更高的糖胺聚糖含量（每毫克湿重13.8±1.2微克对每毫克湿重8.2±0.8微克，p<0.001）和胶原蛋白含量（每毫克湿重10.2±0.9微克对每毫克湿重6.8±0.6微克，p<0.001）。组织学分析显示，动态加载的圆盘具有更均匀的细胞分布和更有序的细胞外基质沉积，类似于天然关节软骨。这些结果表明，生理应变水平的动态变形加载可显著增强细胞接种琼脂糖支架中的软骨细胞基质合成，为改善组织工程软骨的力学性能提供了一种潜在的策略。
Due to its avascular nature, articular cartilage exhibits a very limited capacity to regenerate and to repair. Although much of the tissue-engineered cartilage in existence has been successful in mimicking the morphological and biochemical appearance of hyaline cartilage, it is generally mechanically inferior to the natural tissue. In this study, we tested the hypothesis that the application of dynamic deformational loading at physiological strain levels enhances chondrocyte matrix elaboration in cell-seeded agarose scaffolds to produce a more functional engineered tissue construct than in free swelling controls. A custom-designed bioreactor was used to load cell-seeded agarose disks dynamically in unfolded compression with a peak-to-peak compressive strain amplitude of 10 percent, at a frequency of 1 Hz, 3 X (1 hour on, 1 hour off)/day, 5 days/week for 4 weeks. Results demonstrated that dynamically loaded disks yielded a sixfold increase in the equilibrium aggregate modulus over free swelling controls after 28 days of loading (100 +/- 16 kPa versus 15 +/- 8 kPa, p