Background. As articular cartilage is unable to repair itself, there is a tremendous clinical need for a tissue engineered replacement tissue. Current tissue engineering efforts using the self-assembly process have demonstrated promising results, but the biomechanical properties remain at roughly 50% of native tissue. Methodology/Principal Findings. The objective of this study was to determine the feasibility of using exogenous crosslinking agents to enhance the biomechanical properties of a scaffoldless cartilage tissue engineering approach. Four crosslinking agents (glutaraldehyde, ribose, genipin, and methylglyoxal) were applied each at a single concentration and single application time. It was determined that ribose application resulted in a significant 69% increase in Young's modulus, a significant 47% increase in ultimate tensile strength, as well as a trend toward a significant increase in aggregate modulus. Additionally, methylglyoxal application resulted in a significant 58% increase in Young's modulus. No treatments altered the biochemical content of the tissue. Conclusions/Significance. To our knowledge, this is the first study to examine the use of exogenous crosslinking agents on any tissue formed using a scaffoldless tissue engineering approach. In particular, this study demonstrates that a one-time treatment with crosslinking agents can be employed effectively to enhance the biomechanical properties of tissue engineered articular cartilage. The results are exciting, as they demonstrate the feasibility of using exogenous crosslinking agents to enhance the biomechanical properties without the need for increased glycosaminoglycan (GAG) and collagen content.

中文翻译：

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外源性交联剂对自组装组织工程软骨结构生物力学性能的有益影响

背景。由于关节软骨无法自我修复，因此对组织工程替代组织存在巨大的临床需求。当前使用自组装过程的组织工程工作已显示出可喜的结果，但生物力学特性仍约为天然组织的 50%。方法论/主要发现。本研究的目的是确定使用外源性交联剂增强无支架软骨组织工程方法的生物力学性能的可行性。四种交联剂（戊二醛、核糖、京尼平和甲基乙二醛）分别以单一浓度和单一施用时间施用。经确定，核糖应用导致杨氏模量显着增加 69%，极限抗拉强度显着增加了 47%，以及总模量显着增加的趋势。此外，甲基乙二醛应用导致杨氏模量显着增加 58%。没有治疗改变组织的生化含量。结论/意义。据我们所知，这是第一项研究在使用无支架组织工程方法形成的任何组织上使用外源交联剂的情况。特别是，这项研究表明，一次性使用交联剂处理可以有效地提高组织工程关节软骨的生物力学性能。结果令人振奋，