Composite Hydrogels and Their Mechanisms to Inhibit Matrix Mineralization by Hypertrophic Chondrocytes

摘要

We have developed materials that can be used to maintain cartilage or drive mineralization. These results indicate that PGH hydrogels support hypertrophic differentiation of chondrocytes but inhibit their terminal differentiation, confirmed by the apoptosis data. The PGH hydrogels inhibit mineralization by interfering in the timing of deposition of the necessary matrix factors Coll, Col 10, and ALP. These material effects may arise from two mechanisms. First, the PGH hydrogel has less hydrolyzed collagen (gelatin) content than GEL, while more inhibitor of gelatinases (Timp3). Collagen fragments promote hypertrophy; gelatin fragments in GEL may have a similar effect. We are investigating MMP inhibition to test this theory. Second, PGH has more heparin than GEL. Heparin binds to bioactive molecules (e.g. TGFβs) and enhances their signaling. This may promote cartilage matrix production and suppress chondrocyte terminal differentiation. To test these theories, we will perform integrin profiling and analyze key markers of potentially affected signaling pathways.