Black phosphorus nanosheets in orthopedics: from material fabrications to therapeutic prospects

In recent years, the incidence of orthopedic diseases has increased significantly, while traditional treatments often face limitations such as limited efficacy and pronounced side effects. The development of nanomedicine technology provides novel strategies for orthopedic disease treatment. As an emerging two-dimensional nanomaterial, black phosphorus nanosheets (BPNSs) demonstrate remarkable potential in the treatment of orthopedic diseases due to their unique physicochemical properties, superior biocompatibility, and the fact that their degradation product-elemental phosphorus-constitutes an essential component of bone tissue. This review systematically summarizes the fundamental properties of BPNS, their preparation methods (mechanical exfoliation, chemical vapor deposition, liquid exfoliation, and electrochemical exfoliation), and functional modification strategies (surface covalent coupling, ion loading, and surface coating). We then focus on analyzing research progress in multiple clinical orthopedic applications including bone regeneration, bone defect repair, treatment of degenerative bone diseases, bone tumor therapy, wound healing promotion and orthopedic image-guided applications. Simultaneously, this review objectively discusses key challenges facing clinical translation of BPNS, including long-term biosafety concerns, large-scale preparation technology limitations, and insufficient mechanistic studies, while proposing future research directions. We believe that with further advancements in materials science, nanotechnology, and biomedical engineering, BPNS will become a novel nanomedicine in orthopedic treatment, offering patients more effective and safer therapeutic options.