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

ABSTRACT

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.