A Covalently Cross-Linked Hyaluronic Acid/Carboxymethyl Cellulose Composite Hydrogel as a Potential Filler for Soft Tissue Augmentation

The use of fillers for soft tissue augmentation is an approach to restore the structure in surgically or traumatically created tissue voids. Hyaluronic acid (HA), is one of the main components of the extracellular matrix, and it is widely employed in the design of materials with features similar to human tissues. HA-based fillers already find extensive use in soft tissue applications, but are burdened with inherent drawbacks, such as poor thermal stability. A well-known strategy to improve the HA properties is to reticulate it with 1,4-Butanediol diglycidyl ether (BDDE). The aim of this work was to improve the design of HA hydrogels as fillers, by developing a crosslinking HA method with carboxymethyl cellulose (CMC) by means of BDDE. CMC is a water soluble cellulose ether, whose insertion into the hydrogel can lead to increased thermal stability. HA/CMC hydrogels at different ratios were prepared, and their rheological properties and thermal stability were investigated. The hydrogel with an HA/CMC ratio of 1/1 resulted in the highest values of viscoelastic moduli before and after thermal treatment. The morphology of the hydrogel was examined via SEM. Biocompatibility response, performed with the Alamar blue assay on fibroblast cells, showed a safety percentage of around 90% until 72 h.