Structural changes and crosslinking modulated functional properties of oxi-HA/ADH hydrogels useful for regenerative purposes

Partially oxidized hyaluronic acid (oxi-HA) crosslinked with adipic acid dihydrazide (ADH) has been explored as a promising injectable biomaterial for cell-based therapy and regenerative purposes. However, there is a lack of basic scientific studies and medical applications to support the technological approaches and optimizations of these biomaterials. Thus, we provided a relationship connecting the structural changes to the functional properties, which are modulated by the oxi-HA oxidation degree and ADH crosslinking. Oxi-HA was obtained from the reaction with sodium periodate (NaIO4), which oxidizes the proximal hydroxyl in aldehydes groups by opening the sugar ring and promoting macromolecular compaction. The results showed that the oxi-HA oxidation degree caused the structural changes that increased the zeta potential and decreased the hydrodynamic volume and viscosity. Therefore, the extrusion force, injectability, and ADH crosslinking were benefited by the click chemistry. Additionally, the ADH concentration modulated the functional properties such as the swelling, stability, gelation time and thermosensitivity of the oxi-HA/ADH hydrogels. These results are relevant for supporting the design and optimization of novel hyaluronic acid-based formulations for applications in the broad field of tissue regeneration.