Black Phosphorus Hydrogel Scaffolds Enhance Bone Regeneration via a Sustained Supply of Calcium-Free Phosphorus

Effective bone regeneration remains a challenge for bone-tissue engineering. In this study, we propose a new strategy to accelerate bone regeneration via a sustained supply of phosphorus without providing foreign calcium. Herein, a black phosphorus nanosheet (BPN)-based hydrogel platform was developed, and the BPNs were used to stably and mildly provide phosphorus. The hydrogel was fabricated by photo-crosslinking of gelatin methacrylamide, BPNs, and cationic arginine-based unsaturated poly(ester amide)s. This platform combines the following advantages: the hydrogel scaffold would keep BPNs inside, and the encapsulated BPNs can degrade into phosphorus ions and capture calcium ions to accelerate biomineralization in a bone defect. The introduction of BPNs helped to enhance the mechanical performance of hydrogels, photoresponsively release phosphate, and accelerate mineralization in vitro. Moreover, BPN-containing hydrogels improved osteogenic differentiation of human dental pulp stem cells via the bone morphogenic protein-runt-related transcription factor 2 pathway. In vivo results from a rabbit model of bone defects revealed that the BPNs helped to accelerate bone regeneration. All these results strongly suggest that the strategy of a sustained supply of calcium-free phosphorus and this BPN-containing hydrogel platform hold promise for effective bone regeneration.