Concentrically Integrative Bioassembly of a Three-Dimensional Black Phosphorus Nanoscaffold for Restoring Neurogenesis, Angiogenesis, and Immune Homeostasis

Black phosphorus is well known for its excellent electromechanical properties. Although it has previously been used for therapeutic drug delivery in cancer, it has never been applied as an electroactive polymer for post-trauma tissue regeneration (e.g., in cardiac muscles and neurons). The major concern currently preventing such applications is its controversial biosafety profile in vivo. Here, we demonstrate the production of a concentrically integrative layer-by-layer bioassembled black phosphorus nanoscaffold. This scaffold has remarkable electrical conductivity, permitting smooth release into the surrounding microenvironment. We confirmed that, under mild oxidative stress, our black phosphorus nanoscaffold induced angiogenesis and neurogenesis and stimulated calcium-dependent axon regrowth and remyelination. Long-term in vivo implantation of this nanoscaffold during severe neurological defect regeneration induced negligible toxicity levels. These results provide new insight into the regenerative capability of manufactured 3D scaffolds using neuroengineered 2D black phosphorus nanomaterials.