Human cartilage has relatively slow metabolism compared to other normal tissues. Cartilage damage is of great clinical consequence since cartilage has limited intrinsic healing potential. Cartilage tissue engineering is a rapidly emerging field that holds great promise for tissue function repair and artificial/engineered tissue substitutes. However, current clinical therapies for cartilage repair are less than satisfactory and rarely recover full function or return the diseased tissue to its native healthy state. Kartogenin (KGN), a small molecule, can promote chondrocyte differentiation both in vitro and in vivo. The purpose of this research is to optimize the chondrogenic process in mesenchymal stem cell (MSC)-based chondrogenic constructs with KGN for potential use in cartilage tissue engineering. In this study, we demonstrate that KGN treatment can promote MSC condensation and cell cluster formation within a tri-copolymer scaffold. Expression of Acan, Sox9, and Col2a1 was significantly up-regulated in three-dimensional (3D) culture conditions. The lacuna-like structure showed active deposition of type II collagen and aggrecan deposition. We expect these results will open new avenues for the use of small molecules in chondrogenic differentiation protocols in combination with scaffolds, which may yield better strategies for cartilage tissue engineering.

中文翻译：

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Kartogenin增强3D三元共聚物支架和自行设计的生物反应器系统中MSC的软骨分化。

与其他正常组织相比，人软骨的代谢相对较慢。由于软骨具有有限的内在治愈潜力，因此软骨损伤具有重大的临床后果。软骨组织工程是一个快速发展的领域，它对组织功能修复和人工/工程组织替代物具有广阔的前景。然而，目前用于软骨修复的临床疗法并不令人满意，并且很少恢复全部功能或使患病的组织恢复其天然健康状态。Kartogenin（KGN）是一种小分子，可以在体外和体内促进软骨细胞分化。这项研究的目的是优化具有KGN的基于间充质干细胞（MSC）的成软骨构建体中的软骨形成过程，以潜在地用于软骨组织工程中。在这个研究中，我们证明，KGN治疗可以促进MSC冷凝和三共聚物支架内的细胞簇形成。表达Acan，Sox9和Col2a1在三维（3D）培养条件下显着上调。腔状结构显示II型胶原的活跃沉积和聚集蛋白聚糖的沉积。我们希望这些结果将为在与软骨支架相结合的软骨分化方案中使用小分子开辟新途径，这可能会为软骨组织工程提供更好的策略。