Cellular interactions in cell-based cartilage repair

Interactions of cells with their surrounding neighbors and matrix, which most likely involves cell-cell communication, are vital for successful tissue development and regeneration. These interactions are complex due to the involvement of multiple signaling pathways, such as signals mediated by gap-junctions, direct cell-cell contacts and growth factors which simultaneously activated in the same cell. Understanding the cellular communication mechanisms and the regulation of complex intercellular interactions in co-cultures are thus of great importance in cartilage tissue regeneration. In addition, to mimic the hydrated environment of articular cartilage, injectable hydrogels can be used to facilitate cell proliferation, differentiation, and matrix production by encapsulated cells. Moreover, a hybrid injectable hydrogel can combine multiple functionalities, such as tunable physical properties, proteolytic degradation properties, and enhanced extracellular matrix production, into one gel system. Therefore, the optimal concentration and the ratio of polymers-based hybrid hydrogels for cell growth and matrix formation are essential for the application of cell encapsulated injectable bio-constructs for cartilage regeneration.
This thesis describes: i) the fundamental knowledge regarding how mesenchymal stem cells act as a mediator in Chondrocyte-MSC co-cultures and how MSCs can regulate cellular behavior and chondro-induction features in co-cultures; ii) potential cell death mechanisms regulating Chondrocyte-MSC co-cultures and the cellular interactions in co-cultures; and iii) the modification of injectable hydrogels with optimal hybrid polymers and encapsulated cells to improve upon cartilage regeneration strategies.
Altogether, this thesis introduces a set of cellular interactions investigation and innovative hybrid injectable hydrogel modifications. The findings presented in this thesis could facilitate the development of new therapeutic strategies and contribute to the clinical translation of cartilage tissue engineering applications.