Black phosphorus nanosheets fortified with catalase to enhance Schwann cell responses for neural repair

Peripheral nerve injuries (PNI) present a significant clinical challenge due to the complex cellular and molecular activities that hinder functional recovery. Schwann cells (SCs), the principal glial cells in the peripheral nervous system, play a vital role in neural repair by transitioning into a repairing phenotype capable of supporting axonal regrowth. However, these regenerative properties fade over time, leading to poor clinical outcomes. To address this issue, we engineered a black phosphorus nanosheet (BPNS) functionalized with catalase (BPNS@CAT) to modulate SC activity and enhance nerve regeneration. In vitro experiments demonstrated that BPNS@CAT reduced ROS levels, regulated the angiogenic and immunomodulatory functions of SCs. Mechanistically, we identified that BPNS@CAT activated the JAK/STAT pathway, which is crucial for SC-mediated repair processes. To validate its therapeutic potential, a BPNS@CAT-GelMA/PCL hydrogel scaffold was fabricated and applied in a rat sciatic nerve-crush model. The scaffold enhanced axonal regeneration, restored nerve function, and improved sensory, motor, and emotional behaviors. Our study broadens the range of BPNS applications in SC-based nerve repair and pave the way for future applications of BPNS in translational medicine.