Abstract
Between nerve defects, a bridge formed by multiple cells is the fundamental structure for guiding axons across this damaged region. Here, we developed a functional material that mimics hypoxia during the early stages of nerve regeneration by deferoxamine. We used this material and single-cell sequencing to analyze the "bridge" structure between peripheral nerve defects. We found that hypoxia in damaged tissues might play a key role in stimulating macrophages, promoting endothelial-to-mesenchymal transition, and driving the migration of endothelial cells to the injured region to form regenerative bridge tissue and guide the subsequent regeneration of Schwann cells and axons. The results showed that the final nerve defect repair outcomes were similar with autografts after intervention by this material. This study challenges the view that hypoxia is exclusively involved in peripheral nerve regeneration and provides a potentially valuable candidate material for clinical use.