Abstract

Black phosphorus nanosheets (BPNS) are degradable, interface-active nanomaterials with potential applications in bone tissue engineering, yet how their nano–bio interface processes translate into osteogenic regulation in dental-derived stem cells remains unclear. BPNS-assisted osteogenic differentiation of dental follicle stem cells (DFSCs) was evaluated to establish an interface-to-phenotype framework. BPNS formed a protein corona in serum-containing medium, remained stably dispersed without visible aggregation/sedimentation over 48 h, and exhibited time-dependent phosphate release. Confocal imaging showed cellular uptake of Cy3-labeled BPNS with an apparent Golgi-associated intracellular distribution. Functionally, BPNS significantly enhanced DFSC osteogenesis, increasing ALP activity, mineralization, and osteogenic marker expression. Notably, phosphate-matched supplementation based on BPNS release levels failed to reproduce the phenotype, indicating that BPNS-driven osteogenesis is not explained solely by bulk phosphate availability. Mechanistically, circRNA profiling identified circCOG1 as BPNS-responsive; gain-/loss-of-function experiments supported circCOG1 as a positive regulator of DFSC osteogenesis. CircCOG1 directly bound miR-8085, miR-8085 directly targeted the COG1 3′UTR, and rescue experiments supported a circCOG1/miR-8085/COG1 axis contributing to BPNS-enhanced osteogenesis. Collectively, these findings link BPNS nano–bio interface behaviors to osteogenic outcomes and support the potential application of BPNS-enabled DFSC strategies in maxillofacial bone defect repair.