Crosslinking by Click Chemistry of Hyaluronan Graft Copolymers Involving Resorcinol-Based Cinnamate Derivatives Leading to Gel-like Materials

Abstract

The well-known “click chemistry” reaction copper(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC) was used to transform under very mild conditions hyaluronan-based graft copolymers HA(270)-FA-Pg into the crosslinked derivatives HA(270)-FA-TEGERA-CL and HA(270)-FA-HEGERA-CL. In particular, medium molecular weight (i.e., 270 kDa) hyaluronic acid (HA) grafted at various extents (i.e., 10, 20, and 40%) with fluorogenic ferulic acid (FA) residue bonding propargyl groups were used in the CuAAC reaction with novel azido-terminated crosslinking agents Tri(Ethylene Glycol) Ethyl Resorcinol Acrylate (TEGERA) and Hexa(Ethylene Glycol) Ethyl Resorcinol Acrylate (HEGERA). The resulting HA(270)-FA-TEGERA-CL and HA(270)-FA-HEGERA-CL materials were characterized from the point of view of their structure by performing NMR studies. Moreover, the swelling behavior and rheological features were assessed employing TGA and DSC analysis to evaluate the potential gel-like properties of the resulting crosslinked materials. Despite the 3D crosslinked structure, HA(270)-FA-TEGERA-CL and HA(270)-FA-HEGERA-CL frameworks showed adequate swelling performance, the required shear thinning behavior, and coefficient of friction values close to those of the main commercial HA solutions used as viscosupplements (i.e., 0.20 at 10 mm/s). Furthermore, the presence of a crosslinked structure guaranteed a longer residence time. Indeed, HA(270)-FA-TEGERA-CL-40 and HA(270)-FA-HEGERA-CL-40 after 48 h showed a four times greater enzymatic resistance than the commercial viscosupplements. Based on the promising obtained results, the crosslinked materials are proposed for their potential applicability as novel viscosupplements.