Calcium Cross-Linked\nCellulose Nanofibrils: Hydrogel\nDesign for Local and Controlled Nitric Oxide Release

Nitric oxide (NO) holds promise for wound healing due\nto its antimicrobial\nproperties and role in promoting vasodilation and tissue regeneration.\nThe local delivery of NO to target cells or organs offers significant\npotential in numerous biomedical applications, especially when NO\ndonors are integrated into nontoxic viscous matrices. This study presents\nthe development of robust cellulose nanofibril (CNF) hydrogels designed\nto control the release of nitric oxide (NO) generated <i>in situ</i> from a NO-donor molecule (<i>S</i>-nitrosoglutathione,\nGSNO) obtained from the nitrosation of its precursor molecule glutathione\n(GSH). CNF, efficiently isolated from sugar cane bagasse, exhibited\na high aspect ratio and excellent colloidal stability in water. Although\ndepletion forces could be observed upon the addition of GSH, this\neffect did not significantly alter the morphology of the CNF network\nat low GSH concentrations (<20 mM). Ionic cross-linking with Ca<sup>2+</sup> resulted in nontoxic and robust hydrogels (elastic moduli\nranging from 300 to 3000 Pa) at low CNF solid content. The release\nrate of NO from GSNO decreased in CNF from 1.61 to 0.40 mmol. L<sup>–1</sup>·h<sup>–1</sup> when the nanofibril content\nraised from 0.3 to 1.0 wt %. The stabilization effect monitored for\n16 h was assigned to hydrogel mesh size, which was easily tailored\nby modifying the concentration of CNF in the initial suspension. These\nresults highlight the potential of CNF-based hydrogels in biomedical\napplications requiring a precise NO delivery.