Black phosphorus quantum dots pretreated ADSCs promotes bone regeneration coupling of osteogenesis and osteoimmunomodulation

Adipose-derived mesenchymal stem cells (ADSCs) are ideal candidates for regenerative therapy to promote the critical bone defects repair due to their good accessibility, multi-potency capacity and paracrine functions. However, the limited osteogenic differentiation ability and uncertain paracrine function seriously impedes the clinical application of ADSCs in bone regeneration engineering. Herein, we explore the cellular behaviors and osteogenic ability of ADSCs treated with black phosphorus quantum dots (BPQDs). Additionally, macrophage polarization, osteogenic effects and angiogenesis functions are explored through paracrine pathway regulated by BPQDs-pretreated ADSCs. BPQDs show good biocompatibility with ADSCs and BPQDs-pretreated ADSCs can improve osteogenesis process in vivo by promoting osteogenic differentiation and osteoimmunomodulation. In mechanism, BPQDs increase the osteogenic differentiation of ADSCs, which can be regulated via the Wnt/β-catenin and BMP2/SMAD5/Runx2 signaling pathway. On the other hand, BPQDs-pretreated ADSCs promote the osteogenic effect of BMSCs and facilitate the polarization of macrophages from M1 towards M2 phenotype transformation in turn to accelerate the angiogenesis through paracrine pathway. This strategy provides a novel idea for the use of bone tissue engineering in the foreseeable future.