关键词: 纳米纤维素, 抗菌性, 抗氧化性, 水凝胶, 生物医用材料, 羧甲基壳聚糖, 蓝莓花青素, 伤口敷料

Abstract:

Objective Maintaining a moist wound environment, eliminating excessive reactive oxygen species (ROS), preventing bacterial proliferation, and enabling infection monitoring are all essential components in the management of chronic wounds. In order to develop hydrogel dressings with antimicrobial, antioxidative, and infection-monitoring properties, cellulose nanofibers (CNF) were aldehyde-functionalized and crosslinked with carboxymethyl chitosan (CMCS) through a Schiff base reaction to form the hydrogel. Blueberry anthocyanins (BA) were loaded into the hydrogel by electrostatic adsorption and hydrogen bonding, resulting in a cellulose nanofiber-based antimicrobial, antioxidative, and pH-responsive hydrogel dressing for wound infection monitoring.

Method Aldehyde-functionalized cellulose nanofibers (DACNF) were prepared by sodium periodate oxidation. Different dosages of BA were then added to the DACNF solution and mixed thoroughly. Schiff base reactions occurred between the aldehyde groups in DACNF and the amino groups in CMCS, resulting in the formation of a hydrogel. In this system, BA interacted with the molecular chains of DACNF and CMCS through electrostatic adsorption and hydrogen bonding. The microstructure and chemical composition of the obtained hydrogel were characterized, and its water vapor transmission rate, antioxidant properties, antibacterial activity, pH-responsive color change, and cytotoxicity were systematically evaluated.

Results In the infrared spectra, DACNF exhibited a characteristic aldehyde peak compared to CNF, which disappeared after hydrogel synthesis. In the XRD patterns, the diffraction peak at 2θ=22.7° was significantly reduced in DACNF compared to CNF, and the crystallinity decreased from 77.1% to 56.9%. After hydrogel synthesis, the crystallinity further decreased due to the disruption caused by the Schiff base reaction. When the mass fraction of BA in the hydrogel was increased to 0.125%, the pore size notably decreased compared to hydrogel free of BA, as the increased BA content formed more hydrogen bonds. The hydrogel containing 0.125% anthocyanins exhibited a water vapor transmission rate of 2 611.43 g/(m²·24 h), lower than that of the hydrogel without BA, as the addition of BA reduced the pore size. As the anthocyanin content increased, the free radical scavenging efficacy was correspondingly improved, with the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity reaching 66.90%, by virtue of the increase in BA content introducing a large number of phenolic hydroxyl groups, which neutralized some radicals through hydrogen and electron transfer. Antibacterial tests revealed inhibition rates of 97.35% against S.aureus and 97.21% against E.coli for the 0.125% BA hydrogel, which was attributed to the antimicrobial activity of CMCS. At pH=5.5, the hydrogel color changed from blue-purple to red, with an increase in the a value and red saturation. After 20 min, the total color difference (ΔE) reached 8.02, indicating a visually perceptible change. At pH=7.2, the b value increased while blue saturation decreased, resulting in a lighter color. After 20 min, ΔE increased to 6.28, and the color change of the hydrogel could also be visually captured. Cell viabilities at 1, 3, and 7 d were all above 80%, demonstrating the low cytotoxicity of the hydrogel containing BA.

Conclusion The hydrogel containing 0.125% anthocyanins exhibited excellent antibacterial properties, and good inhibition rates of 97.35% against S. aureus and 97.21% against E. coli. Furthermore, it showcased significant pH-responsive color change, presenting red and blue-purple colors in PBS solutions at pH=5.5 and pH=7.2, respectively. Additionally, the hydrogel displayed a notable DPPH free radical scavenging rate of 75.83%. It also exhibited favorable biocompatibility, with cell viability over 80% at 1, 3, and 7 d. Overall, the findings demonstrate that blueberry anthocyanins hold significant potential for developing pH-sensitive wound hydrogels with antioxidant capabilities. They further serve as a significant reference for the development of innovative pH-responsive wound hydrogel dressings.

Key words: cellulose nanofiber, antibacterial, antioxidant, hydrogel, biomedical material, carboxymethyl chitosan, blueberry anthocyanins, wound dressing