Macroscale mesenchymal condensation to study cytokine-driven cellular and matrix-related changes during cartilage degradation.

Understanding the pathophysiological processes of cartilage degradation requires adequate model systems to develop therapeutic strategies towards osteoarthritis (OA). Although differentin vitroorin vivomodels have been described, further comprehensive approaches are needed to study specific disease aspects. This study aimed to combinein vitroandin silicomodeling based on a tissue-engineering approach using mesenchymal condensation to mimic cytokine-induced cellular and matrix-related changes during cartilage degradation. Thus, scaffold-free cartilage-like constructs (SFCCs) were produced based on self-organization of mesenchymal stromal cells (mesenchymal condensation) and (i) characterized regarding their cellular and matrix composition or secondly (ii) treated with interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF alpha) for 3 weeks to simulate OA-related matrix degradation. In addition, an existing mathematical model based on partial differential equations was optimized and transferred to the underlying settings to simulate the distribution of IL-1 beta, type II collagen degradation and cell number reduction. By combiningin vitroandin silicomethods, we aimed to develop a valid, efficient alternative approach to examine and predict disease progression and effects of new therapeutics.