Calcium Cross-Linked Cellulose Nanofibrils: Hydrogel Design for Local and Controlled Nitric Oxide Release

Nitric oxide (NO) holds promise for wound healing due to its antimicrobial properties and role in promoting vasodilation and tissue regeneration. The local delivery of NO to target cells or organs offers significant potential in numerous biomedical applications, especially when NO donors are integrated into nontoxic viscous matrices. This study presents the development of robust cellulose nanofibril (CNF) hydrogels designed to control the release of nitric oxide (NO) generated <i>in situ</i> from a NO-donor molecule (<i>S</i>-nitrosoglutathione, GSNO) obtained from the nitrosation of its precursor molecule glutathione (GSH). CNF, efficiently isolated from sugar cane bagasse, exhibited a high aspect ratio and excellent colloidal stability in water. Although depletion forces could be observed upon the addition of GSH, this effect did not significantly alter the morphology of the CNF network at low GSH concentrations (<20 mM). Ionic cross-linking with Ca²⁺ resulted in nontoxic and robust hydrogels (elastic moduli ranging from 300 to 3000 Pa) at low CNF solid content. The release rate of NO from GSNO decreased in CNF from 1.61 to 0.40 mmol. L^-1·h^-1 when the nanofibril content raised from 0.3 to 1.0 wt %. The stabilization effect monitored for 16 h was assigned to hydrogel mesh size, which was easily tailored by modifying the concentration of CNF in the initial suspension. These results highlight the potential of CNF-based hydrogels in biomedical applications requiring a precise NO delivery.