Development of a thermosensitive statin loaded chitosan-based hydrogel promoting bone healing

Statins have been proposed as potential adjuvant to periodontal treatment due to their pleiotropic properties. A new thermosensitive chitosan hydrogel loaded with statins (atorvastatin and lovastatin) nanoemulsions was synthesized to allow a spatially controlled local administration of active compounds at lesion site. Spontaneous nano-emulsification method was used to synthesize statins loaded nanoemulsions. In vitro, atorvastatin and lovastatin loaded nanoemulsions were cytocompatible and were able to be uptake by oral epithelial cells. Treatment of Porphyromonas gingivalis infected oral epithelial cells and gingival fibroblasts with atorvastatin and lovastatin loaded nanoemulsions decreased significantly pro-inflammatory markers expression (TNF-α and IL-1β) and pro-osteoclastic RANKL. Nevertheless, such treatment induced the expression of Bone sialoprotein 2 (BSP2) in osteoblast emphasizing the pro-healing properties of atorvastatin and lovastatin nanoemulsions. In vivo, in a calvarial bone defect model (2 mm), treatment with the hydrogel loaded with atorvastatin and lovastatin nanoemulsions induced a significant increase of the neobone formation in comparison with systemic administration of statins. This study demonstrates the potential of this statins loaded hydrogel to improve bone regeneration and to decrease soft tissue inflammation. Its use in the specific context of periodontitis management could be considered in the future with a reduced risk of side effects.