Development of a thermosensitive hydrogel loaded with DTT and SDF-1 facilitating in situ periodontal bone regeneration

Abstract

• P. gingivalis infection causes increased ROS level and inhibits osteoblast activity. • A multifunctional thermosensitive hydrogel was prepared with PEG-DA, DTT and SDF-1. • The hydrogel achieved co-therapy effect by combined application of DTT and SDF-1. • The hydrogel facilitated in situ periodontal bone regeneration in periodontitis rat. • The co-therapy strategy and the hydrogel are promising for regenerative medicine. Periodontitis is characterized by local inflammatory response and alveolar bone resorption induced by pathogenic microorganisms colonization. The increase in reactive oxygen species (ROS) levels not only aggravates the local inflammation, but also inhibits the process of osteogenesis. The coupled process of reducing ROS level and reshaping the activity of osteoblasts is prerequisite to facilitate in situ periodontal tissue regeneration. In this study, we developed a thermosensitive hydrogel loaded with dithiothreitol (DTT) and stromal cell-derived factor-1 (SDF-1) and explored its effect on reshaping osteoblasts activity and facilitating periodontal bone regeneration. In vitro , the hydrogel PEGD@SDF-1 significantly reduced cellular ROS levels, reactivated the Wnt/β-catenin pathway of osteoblasts and restored their osteogenic ability in an inflammatory state. In vivo , the hydrogel PEGD@SDF-1 was applied in rat periodontitis models and showed satisfactory effects on reducing the level of ROS damage, reactivating the Wnt/β-catenin pathway, alleviating the inflammation level, and promoting the periodontal bone regeneration, simultaneously. Taken together, these results suggest that the combined application of DTT and SDF-1 facilitates in situ periodontal tissue regeneration and the thermosensitive hydrogel PEGD@SDF-1 is a promising candidate for periodontal therapy.