A Novel Double Network Hydrogel Promotes Periodontal Tissue Regeneration

The irreversible destruction of the periodontium remains to be the crux of periodontal therapy. Excessive reactive oxygen species (ROS) accumulation and anatomically intricate bone defects constrain the development of therapeutic strategies. Thus, this research aimed to explore a novel drug delivery platform to provide therapeutic options for modulating oxidative stress microenvironment and promoting bone regeneration. The injectable double-crosslinking hyaluronic acid hydrogel loaded with metformin (HA-DAB@Met) was synthesized based on ① Diels–Alder reaction between methylfuran and maleimide. ②Boronic ester dynamic covalent bond between phenylboronic acid and polyvinylalcohol (PVA). The physicochemical properties of HA-DAB@Met hydrogel were characterized by scanning electron microscopy (SEM), 1HNMR, swelling ability, degradation properties, and metformin release properties. The HA-DAB@Met hydrogel was comprehensively evaluated both in vitro and in vivo for its cytotoxicity, osteogenic potential, antioxidant properties and alveolar bone regeneration capacity.All procedures were approved by the Ethics Committee. The results confirmed that the HA-DAB@Met hydrogel had ideal physicochemical properties, rheological tests show that the storage modulus is higher and more suitable than that of single-network hydrogels. In vitro and in vivo studies demonstrated that the HA-DAB@Met hydrogel significantly upregulated osteogenic gene/protein expression, enhanced alkaline phosphatase activity, effectively scavenged ROS and promoted extracellular matrix mineralization in MC3T3-E1 cells and rat periodontitis model. Results of this study indicate that HA-DAB@Met hydrogel had significant antioxidant capacity and exciting potential for promoting alveolar bone regeneration.