Sulfonated Hyaluronic Acid-Based Polymers and Hydrogels Using Thiol-Ene and Thiol-Michael Reactions

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Tissue Engineering

Background:

• Non-sulfated polysaccharides like hyaluronic acid (HA) are explored for tissue engineering scaffolds.
• Mimicking sulfated glycosaminoglycans requires sulfate grafting, but harsh conditions cause degradation.
• Sulfonates offer a sulfate-like function but haven't been applied to polysaccharides.

Purpose of the Study:

• To develop a mild, two-step strategy for introducing tunable sulfonate groups onto HA.
• To create HA-based hydrogels with controlled stiffness and sulfonate content.
• To establish a versatile method applicable to other polysaccharides.

Main Methods:

• Grafting norbornene (NB) or maleimide (MAL) onto HA using DMTMM activation.
• Coupling 3-mercapto-1-propanesulfonate (MPS) via thiol-ene and thiol-Michael additions.
• Forming hydrogels using poly(ethylene glycol)-di-SH crosslinker with NB-conjugated HA.

Main Results:

• Tunable sulfonate groups were successfully introduced onto HA without backbone degradation.
• HA-MAL showed poor crosslinking kinetics, limiting its application.
• Hydrogels with tunable stiffness and sulfonate density were formed using NB-conjugated HA and MPS.
• The strategy demonstrated high efficiency and applicability to polysaccharide modification.

Conclusions:

• A simple, efficient strategy for sulfonate modification of HA was established.
• This method overcomes limitations of traditional sulfate grafting for tissue engineering.
• The developed HA-based hydrogels offer tunable properties for biomedical applications.
• The approach is potentially extendable to other polysaccharides, broadening its impact.