Abstract
Managing bone defects remains a formidable clinical hurdle, primarily attributed to the inadequate orchestration of vascular reconstruction and osteogenic differentiation in both spatial and temporal dimensions. This challenge persists due to the constrained availability of autogenous grafts and the limited regenerative capacity of allogeneic or synthetic bone substitutes, thus necessitating continual exploration and innovation in the realm of functional and bioactive bone graft materials. While synthetic scaffolds have emerged as promising carriers for bone grafts, their efficacy is curtailed by deficiencies in vascularization and osteoinductive potential. Nitric oxide (NO) plays a key role in revascularization and bone tissue regeneration, yet studies related to the use of NO for the treatment of bone defects remain scarce. Herein, we present a pioneering approach leveraging a photothermal-responsive system to augment NO release. This system comprises macromolecular mPEG-P nanoparticles encapsulating indocyanine green (ICG) (NO-NPs@ICG) and a mPEG-PA-PP injectable thermosensitive hydrogel carrier. By harnessing the synergistic photothermal effects of near-infrared radiation and ICG, the system achieves sustained NO release, thereby activating the soluble guanylate cyclase (SGC)-cyclic guanosine monophosphate (cGMP) signaling pathway both in vitro and in vivo. This orchestrated cascade culminates in the facilitation of angiogenesis and osteogenesis, thus expediting the reparative processes in bone defects. In a nutshell, the NO release-responsive system elucidated in this study presents a pioneering avenue for refining the bone tissue microenvironment and fostering enhanced bone regeneration.