Sulfonated hyaluronic acid-based polymers and hydrogels using thiol-ene and thiol-Michael reactions

To mimic the function of sulfated glycosaminoglycan in the matrix, sulfate groups can be grafted. However, here, harsh reaction conditions are required which induce significant backbone degradation.

As an alternative, sulfonates (R-SO3-) have been shown to resemble the function of sulfates yet have not been introduced on polysaccharides. Using a two-step strategy, we introduced a tunable amount of sulfonate groups on HA, without requiring harsh reaction conditions and organic solvents. By varying the degree of carboxylic acid activation using 4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM), norbornene (NB, 3–18%) or maleimide (MAL, 2–14%) groups were grafted.