On the synthesis and characterization of biofunctional hyaluronic acid based injectable hydrogels for the repair of cartilage lesions

Injectable methacrylated hyaluronic acid (MeHA) hydrogels for the repair of cartilage lesions were synthesized using two different crosslinking methods, namely, a redox initiation system (i.e., ammonium persulfate, APS, and N,N,N,N'-tetramethylenediamine, TEMED) and a matrix metalloproteinase 7 (MMP7)-degradable peptide. The effects of molecular weight of HA, degree of methacrylation (DM) or/and biofunctionalization of MeHA (i.e., with a chondroitin sulfate (CS) binding peptide) on the end-use properties of synthesized hydrogels were experimentally investigated. It was found that the storage modulus (G') of the hydrogels synthesized, using a redox initiation system (i.e., APS and TEMED), increased as the DM of MeHA or/and the molecular weight of HA increased, resulting in the formation of more rigid hydrogels exhibiting a lower degree of swelling and a slower hydrogel degradation rate. The functionalization of MeHA with a CS binding peptide resulted in an increase of the gelation onset time as well as in a decrease of the hydrogel crosslinking density (i.e., resulting in the formation of softer hydrogels). Moreover, it was found that as the concentration of the peptide crosslinker increased the hydrogel onset time decreased as well as the degradation rate of the synthesized hydrogels while their storage modulus (G') increased. Finally, it was found that when the MeHA crosslinking reaction was carried out in a cell growth medium the storage modulus of the hydrogel increased to a value that favored the differentiation of human mesenchymal stem cells (hMSCs) to chondrocytes.