Multifunctional Hyaluronic Acid-Based Hydrogels for Tissue Regeneration

Dynamic covalent hydrogels are a fundamental tool in biomedical engineering for delivering therapeutics to an injury site and providing a favorable environment for tissue regeneration. Our lab produced two hyaluronic acid (HA)-based hydrogels and optimized their physicochemical properties for the repair of injured tissues in the musculoskeletal and central nervous systems. HA was modified with adipic acid dihydrazide (ADH) for crosslinking with either oxidized HA or oxidized alginate to fabricate two hydrazone-crosslinked hydrogels (HA-HA and HA-Alg). Using response surface modeling, we optimized the gelation time, compressive modulus, and rate of swelling/degradation of the hydrogels for each application by varying these input parameters: polymer molecular weight, oxidized polymer content, and ADH-modified polymer content. We also modified HA with norbornene to functionalize the hydrogels with cysteine-terminated peptides to enhance cell-material interactions and incorporate tunable protein-material affinity interactions to control therapeutic protein delivery. We have also demonstrated that these hydrogels provide a favorable environment for cell growth and differentiation. Overall, our dynamic covalent hydrogels are multifunctional and can be used to accelerate the repair of multiple target tissues.