Nerve Regeneration Potential of Antioxidant-Modified Black Phosphorus Quantum Dots in Peripheral Nerve Injury

Peripheral nerve injury is a major societal concern. Black phosphorus (BP) has inherent advantages over cell-based therapies in regenerative medicine. However, controlling spontaneous degradation and size-dependent cytotoxicity remains challenging and poses difficulties for clinical translation. In this study, we constructed zero-dimensional BP quantum dots (QDs) modified with antioxidant β-carotene and comprehensively investigated them in Schwann cells (SCs) to elucidate their potential for peripheral nerve repair. In vitro experiments demonstrated that BPQD@β-carotene has an inappreciable toxicity and good biocompatibility, favoring neural regrowth, angiogenesis, and inflammatory regulation of SCs. Furthermore, the PI3K/Akt and Ras/ERK1/2 signaling pathways were activated in SCs at the genetic, protein, and metabolite levels. The BPQD@β-carotene-embedded GelMA/PEGDA scaffold enhanced functional recovery by promoting axon remyelination and regeneration and facilitating intraneural angiogenesis in peripheral nerve injury models of rats and beagle dogs. These results contribute to advancing knowledge of BP nanomaterials in tissue regeneration and show significant potential for application in translational medicine.