Oral microalgal nanoparticle hydrogel for multifaceted management of chronic oral ulcers in diabetes

The treatment of chronic oral ulcer healing, particularly in diabetic patients, presents a significant clinical challenge. Current therapeutic strategies have inadequately addressed the complexities associated with diabetic oral ulcers, underscoring the urgent need for innovative solutions. In this study, nanoparticles were extracted from edible spirulina powder (SP-NPs) and incorporated into adhesive chitosan-based oral gel (CSgel), resulting in the development of an advanced functional hydrogel (SP-NPs@CSgel) designed to manage chronic oral ulcers in diabetes. The SP-NPs, rich in proteins involved in antioxidant and anti-inflammatory processes, demonstrated significant potential in repairing cellular damage by mitigating oxidative stress and modulating inflammation through the inhibition of the NF-κB pathway in macrophages, with the percentage of M2 macrophage increasing to 27% versus merely 12% in the control group. Additionally, the CSgel exhibited excellent injectable and adhesive properties, which prolonged the retention of SP-NPs in the oral mucosa for over 8 h, representing a four-fold increase compared to merely 2 h for free SP-NPs, thereby significantly accelerating the healing of chronic oral ulcers with complete wound closure achieved within 8 days in diabetic rats and 14 days in diabetic mice with severe ulcers. Furthermore, the SP-NPs@CSgel showed promising effects in alleviating depression-related behaviors and regulating the oral microbiota in severe oral ulcers, creating a conducive environment for ulcer healing. In conclusion, by harnessing the synergistic effects of edible SP-NPs and adhesive CSgel, this hydrogel system represents a safe and effective approach with substantial potential for clinical transformation, offering a promising solution for chronic oral ulcer management in diabetic patients.