Influence of Fibrinogen Concentration on Mesenchymal Stem Cells and Chondrocytes Chondrogenesis in Fibrin Hydrogels

As scaffolding material, fibrin hydrogel has been used for the treatment of cartilage defects, for the implantation of both chondrocytes and mesenchymal stem cells (MSC). Despite the known influence of fibrinogen concentration to stiffness and porosity of the fibrin hydrogel, the impact of fibrinogen concentration in fibrin hydrogel to chondrocyte or stem cell chondrogenic outcome has remained unexplored. By varying fibrinogen concentration, creating fibrin hydrogel of varying stiffness and pore-size, we examine the ability of these fibrin hydrogels to support chondrogenic differentiation of the encapsulated MSC and chondrocyte, and the trophic effect of hydrogel-encapsulated MSC to support chondrocyte cartilage formation in non-contact co-culture. Chondrocytes were able to generate substantial cartilaginous matrix in fibrin hydrogel formulated with wider range of fibrinogen concentration (6-50 mg/ml). In contrast, MSC are highly sensitive to fibrinogen concentration. MSC chondrogenic differentiation was inhibited with increase fibrinogen concentration, and the ability to generate chondrogenic trophic factors were inhibited at 50 mg/ml. This study demonstrates the importance of thorough evaluation of material influence to both differentiation capacity and paracrine trophic effect of MSC in order to maximize the therapeutic potential of MSC for cartilage regeneration.