Simvastatin encapsulated in exosomes can enhance its inhibition of relapse after orthodontic tooth movement

Relapse after orthodontic treatment is a major clinical issue in the dental field. Studies indicate that simvastatin may, to some extent, decrease the rate and magnitude of relapse status. Recent evidence demonstrated that exosome-based drug delivery has a broad prospect of clinical application. Hence, this study investigates whether simvastatin encapsulated in exosomes can inhibit relapse after orthodontic tooth movement (OTM).Periodontal ligament stem cells (PDLSCs) and their exosomes (PDLSCs-Exo) were isolated and identified. Exosomal simvastatin was obtained by co-incubation of simvastatin and PDLSCs-Exo. An OTM rat model was established. During the relapse period, rats' local alveolar bone was injected with simvastatin, PDLSCs-Exo, and exosomal simvastatin to examine the effect on relapse. Finally, we analyzed the influence of exosomal simvastatin on osteogenesis at the molecular and histologic levels.PDLSCs and PDLSCs-Exo were successfully extracted and characterized by multiple means. Simvastatin encapsulated in exosomes can increase the solubility of the drug. Exosomal simvastatin can enhance its inhibition of relapse after OTM in the rat model. The expression level of osteogenic-related genes and proteins in the exosomal simvastatin group is higher than in other groups. Histologic analysis showed a reduction of bone-resorptive lacunae in the exosomal simvastatin group.Encapsulating simvastatin into the exosomes derived from PDLSCs can improve simvastatin solubility and enhance the inhibition effect of relapse in the rat model of OTM. Notably, local injection of PDLSCs-Exo alone can also block the relapse after OTM.