Characterization and optimization of in vitro chondrogenesis and terminal chondrogenic differentiation of porcine and human mesenchymal stem cells embedded in hydrogels under mechanical loading

关节内创伤性软骨损伤导致人类急性制动和慢性生活质量下降。细胞种植支架是治疗此类缺陷的一种可能性。基于透明质酸(HA)的细胞载水凝胶可以解决固体支架的一些缺点，特别是在应用方面。虽然软骨细胞是一种常用的细胞型，但间充质干细胞(MSCs)具有一定的优势。在这一应用中，软骨分化的MSCs肥大是一种负面的副作用，在细胞结构的骨化感觉以后的临床使用。本研究的目的是优化MSC种子HA水凝胶，使其暴露于不同剂量和持续时间的促软骨细胞体液因子中，以确定预培养的理想剂量和时机，以最大限度地提高体外软骨形成活性。促进软骨分化间充质干细胞肥大的机制将被识别和表征。同时，我们希望评估动态机械负荷的协同效应，并研究机械负荷下软骨分化的MSCs在HA水凝胶中的肥大行为。这一研究目标代表了一种基本的科学方法，如果成功实施，可能会迅速转化为临床实践。

Intraaarticular traumatic cartilage defects lead to acute immobilization and chronic decrease of quality of life in humen. Cell-seeded scaffolds are one possibility in the treatment of such defects. Some disadvantages of solid scaffolds especially the application may be solved by using cell-loaded hydrogels based on hyaluronic acid (HA). While chondrocytes are a commonly used cell-type mesenchymal stem cells (MSCs) offer some advantages. In this application hypertrophy of chondrogenic differentiatied MSCs is a negative side effect for later clinical use in sense of ossifications of the cell constructs.The objective of the research project is to optimize MSC-seeded HA hydrogels with exposure to varying doses and durations to pro-chondrogenic humoral factors in order to determine the ideal dose and timing of pre-culture to maximize chondrogenic activity in vitro. Mechanisms, that enhance hypertrophy of chondrogenically differentiated MSCs, will be identified and characterized. Concurrently we want to assess the synergistic effects of dynamic mechanical loading and to characterize hypertrophic behaviour of chondrogenic differentiated MSCs in HA hydrogels under mechanical loading.This research objective represents a basic science approach which may be translated quickly into clinical practice if carried out succesfully.