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

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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.