Injectable Hydrogel Loaded with Magnolol and Nanohydroxyapatite for Treating Periodontitis in Diabetes

Under the influence of diabetes, patients with periodontitis are not only prone to refractory infections, local oxygenation imbalances, and persistent inflammatory reactions in the periodontal tissues but also often suffer from insufficient neo-alveolar bone formation and secondary bone resorption, which makes the treatment of periodontitis with diabetes a major clinical challenge. In this study, a CMOC hydrogel was synthesized via the Schiff base reaction between carboxymethyl chitosan (CMCS) and oxidized carboxymethyl cellulose (OCMC), and subsequently, Magnolol nanoparticles (MAG-NCs) and nanohydroxyapatite (nHA) were encapsulated in it to construct the MAG/nHA/CMOC injectable hydrogel. The hydrogel exhibits good injectable and self-healing properties, which enable it to adapt to irregular alveolar bone absorption in deep periodontal pockets, and the MAG carried in it could achieve a continuous release of 95.51% within 72 h. In vitro experiments showed that the MAG/nHA/CMOC hydrogel has great antibacterial effects on <i>Porphyromonas gingivalis</i> (<i>P. gingivalis</i>), the key periodontal pathogenic bacteria, and it could effectively scavenge reactive oxygen species (ROS), inhibit the expression of M1-type macrophage markers and upregulate the expression of M2-type markers, and promote the differentiation of human periodontal membrane stem cells (hPDLSCs) into osteoblasts. In addition, the MAG/nHA/CMOC hydrogel still demonstrated outstanding anti-inflammatory and bone-promoting effects in the rat model of diabetic periodontitis, remarkably promoting periodontal repair and regeneration in diabetic periodontitis. In summary, the MAG/nHA/CMOC injectable hydrogel developed by this research provides a new personalized strategy for the treatment of diabetic periodontitis by combining the control of infection and inflammation, scavenging excessive ROS, and promoting periodontal tissue repair.