Articular cartilage has a limited capacity for repair or regeneration. While there are a multitude of factors involved in cartilage function and repair, we propose that it is critical to understand the basic endogenous signaling mechanisms among chondrocytes in an engineered construct. An anabolic protein of particular interest is insulin-like growth factor-1 (IGF-1) because it aids in cartilage matrix production, specifically type II collagen expression. Therefore, we have begun to investigate how construct properties affect the insulin-like growth factor-1 (IGF-1) signaling pathway.

Chondrocytes embedded in alginate express IGF-1. Previous studies have demonstrated that in high concentrations of alginate, an up-regulation of IGF-1 expression is observed when decreasing paracrine signaling distances (increasing cell density) occurs. This suggests that high cell density and high matrix content enhances IGF-1 competition. Previous studies have also shown that by delivering exogenous IGF-1 to embedded chondrocytes in alginate leads to a decrease in endogenous IGF-1 expression and an increase in IGF-1 receptor (IGF-1R) expression. This result indicates that chondrocytes may increase the expression of IGF-1R to optimize IGF-1 signaling.

Our current work further extends our understanding of how the IGF-1 signaling pathway is altered by incorporating hyaluronic acid (HA) into alginate hydrogels. Hyaluronic acid is a major extracellular matrix that aids in proteoglycan production by chondrocytes through the receptor CD44. However, little is known about HA affects on the IGF-1 signaling pathway. Therefore, we investigated the effect of hyaluronic acid concentration (0, 0.5 mg/mL and 5.0 mg/mL) in alginate hydrogels upon IGF-1 and IGF-1R expression as well as its correlation with CD44 expression in both an in vitro model and in vivo model (subcutaneously implanted in SCID mice). Additionally, we induced the samples with exogenous IGF-1 (100 ng/mL) to further investigate how this delivery affects expression levels of IGF-1, IGF-1R and CD44 of chondrocytes embedded in the alginate-HA hydrogels. The results of this work indicate how extracellular matrix molecules impact the expression of IGF-1 signaling molecules by chondrocytes, demonstrating that the IGF-1 signaling pathway is affected by modifying the properties of an engineered construct.