MSC Membrane‐Coated circPROSC‐siRNA Nanoparticles for Ameliorating Craniosynostosis by Inhibiting Premature Suture Ossification

Craniosynostosis is a congenital craniofacial disorder caused by excessive osteogenic differentiation of mesenchymal stem cells (MSCs) within cranial sutures. Due to incompletely understood regulatory mechanisms, effective solutions for early diagnosis and minimally invasive therapy remain lacking. In this study, plsama circPROSC is first identified as an independent risk factor for craniosynostosis. Through MSCs osteogenic differentiation and nude mouse ectopic bone formation assays, circPROSC promotes osteogenesis via miR-6815-5p-mediated modulation of the Wnt signaling pathway. Furthermore, MSC membrane-coated siRNA nanoparticles (MM@Lipo/siRNA) targeting circPROSC (si-circPROSC) have been developed to inhibit its expression in the coronal suture by postnatal cranial microinjection, which attenuated premature coronal suture closure in a craniosynostosis mouse model. Collectively, this study provides the first evidence that circPROSC is a promising diagnostic marker and a potential therapeutic target for craniosynostosis.