A supramolecular injectable hydrogel based on β-cyclodextrin-grafted alginate and pluronic-amine loaded with kartogenin for chondrogenic differentiation of mesenchymal stem cells

Abstract

Abstract Owing to the similarity of hydrogels to cartilage extracellular matrix, they have been extensively utilized in the chondral lesions. Moreover, their tunable administration properties are desirable for reducing injuries in lesion sites. Generally, injectable hydrogels are mechanically weak, requiring some modifications for being used as a cell carrier in place of articular cartilage. In this study, a combination of β-cyclodextrin-grafted alginate (Alg-β-CD) and pluronic-amine with multiple physical crosslinking was used for the first time. Supramolecular interactions, including electrostatic forces, host-guest interaction, and hydrophobic interaction with increasing temperature maintain injectability of hydrogels while these interactions boost mechanical properties to the extent that shear modulus surpassed 40 kPa. Vacant β-CD cavities in conjunction with gel network were exploited for kartogenin (KGN) loading. All groups had gel time of less than one minute and gel temperature was 28 °C. No toxic effect of hydrogels on encapsulated cells was observed. While the optimum combination of polymers provided a sustainable release for KGN, it also extended the in vitro degradation time of hydrogels from six days to two weeks. KGN facilitated encapsulated mesenchymal stem cells differentiation towards chondrocytes. Taken together, the synthesized hydrogel proved to be a promising candidate for being utilized in cartilage regeneration.