Jung Youngmee, Kim Soo Hyun, Kim Sang-Heon, Kim Young Ha, Xie Jun, Matsuda Takehisa, Min Byoung Goo
Biomaterials Research Center, Korea Institute of Science and Technology, P.O. Box 131, Cheongryang, Seoul 136-650, South Korea.
J Biomater Sci Polym Ed. 2008;19(1):61-74. doi: 10.1163/156856208783227712.
It is known that complex loading is involved in the development and maintenance of articular cartilage in the body. It means the compressive mechanical stimulation is a very important factor for formation of articular cartilage using a tissue-engineering technique. The objective of this study is to engineer cartilaginous constructs with mechano-active scaffolds and to evaluate the effect of dynamic compression for regeneration of cartilage. The mechano-active scaffolds were prepared from a very elastic poly(L-lactide-co-epsilon-caprolactone) (PLCL) with 85% porosity and 300-500 mum pore size using a gel-pressing method. The scaffold was seeded with 2 x 10(6) chondrocytes and the continuous compressive deformation of 5% strain was applied with 0.1 Hz for 10 days and 24 days, respectively. Then, the chondrocytes-seeded constructs were implanted subcutaneously into nude mice. Mechano-active scaffolds with complete rubber-like elasticity showed almost complete (over 97%) recovery at an applied strain of up to 500%. The amount of chondral extracellular matrix was increased significantly by mechanical stimulation on the highly elastic mechano-active scaffolds. Histological analysis showed the mechanically stimulated implants formed mature and well-developed cartilaginous tissue, as evidenced by the chondrocytes within lacunae and the abundant accumulation of sulfated GAGs. However, unhealthy lacunae shapes and hypertrophy forms were observed in the implants stimulated mechanically for 24 days, compared with those stimulated for 10 days. In conclusion, the proper periodical application of dynamic compression can encourage chondrocytes to maintain their phenotypes and enhance the production of GAGs, which would improve the quality of cartilaginous tissue formed both in vitro and in vivo.
众所周知，复杂载荷参与了体内关节软骨的发育和维持。这意味着压缩机械刺激是利用组织工程技术形成关节软骨的一个非常重要的因素。本研究的目的是用具有机械活性的支架构建软骨组织，并评估动态压缩对软骨再生的影响。采用凝胶压制法，由孔隙率为85%、孔径为300 - 500μm的高弹性聚（L-丙交酯-共-ε-己内酯）（PLCL）制备具有机械活性的支架。将2×10⁶个软骨细胞接种到支架上，分别以0.1Hz的频率施加5%应变的连续压缩变形，持续10天和24天。然后，将接种了软骨细胞的构建体皮下植入裸鼠体内。具有完全橡胶状弹性的机械活性支架在施加高达500%的应变时显示出几乎完全（超过97%）的恢复。在高弹性的机械活性支架上，机械刺激显著增加了软骨细胞外基质的量。组织学分析表明，机械刺激的植入物形成了成熟且发育良好的软骨组织，陷窝内的软骨细胞和硫酸化糖胺聚糖的大量积累证明了这一点。然而，与刺激10天的植入物相比，在机械刺激24天的植入物中观察到了不健康的陷窝形状和肥大形式。总之，适当定期施加动态压缩可以促使软骨细胞维持其表型并增强糖胺聚糖的产生，这将提高体外和体内形成的软骨组织的质量。
