Synthesis and Characterization of Glycosaminoglycan Mimetic Variants to Promote Chondrogenesis

Tissue engineering strategies to treat cartilage damage remain inadequate because of the difficulty in regenerating fully functional cartilage tissue. Sulfated glycosaminoglycans (GAGs), which are found in the native extracellular matrix, are known to interact with growth factors and, thus, promote chondrocyte function. Native GAGs have been explored as viable scaffold materials for tissue repair applications. However, it is unclear what structural features in GAGs are critical for promoting chondrogenesis. Therefore, this study generated GAG mimetics that vary in glycosidic linkage geometry and monomer ring substitution and were evaluated for their effect on mesenchymal stem cell (MSC) chondrogenesis and their potential use in cartilage tissue engineering applications. GAG mimetics were synthesized from cellulose (pSC), starch (SS), and chitin (ChS). pSC has beta-glycosidic linkages, SS has alpha-glycosidic linkages, and ChS has beta-glycosidic linkages and monomers that consist of the amide derivative of glucose. Evaluated in soluble form in MSC pellet cultures, pSC and SS enhanced MSC chondrogenic differentiation as measured by the deposition of chondrogenic matrix components, collagen type II and GAG normalized to the cell number, over ChS and the control culture media (without GAG mimetics). The higher degree of sulfation (DOS) in both the pSC and SS also had an effect on the relative collagen type II deposition and GAG production. These data suggest that beta- and alpha-glycosidic linkages are favorable for promoting chondrogenesis. This study demonstrates the potential of semisynthetic GAG mimetics for chondrogenic differentiation, where structural features should be considered for cartilage repair applications.