Targeting VEGFR2 inhibition within a spatially-confined conduit promotes nerve self-resolution and alleviates mechanical allodynia - PubMed
7 hours ago
- #neuropathic pain
- #VEGFR2 inhibition
- #3D printed microspheres
- Targeting VEGFR2 inhibition within a spatially-confined conduit promotes nerve self-resolution and alleviates mechanical allodynia.
- Stump neuromas cause neuropathic pain due to disorganized axonal regeneration, pathological angiogenesis, scar hyperplasia, and chronic neuroinflammation.
- Current therapies fail to address excessive reactive oxygen species from dysregulated vascular proliferation and activation.
- Developed photo-crosslinked GelMA microspheres functionalized with anti-VEGFR2 peptides (MAVP) to modulate pathological angiogenesis.
- Functionalized microspheres were 3D printed into linear arrays within a spatial-constrictive conduit, promoting nerve end interface self-resolution.
- The system inhibited VEGFR2 phosphorylation, neuroinflammatory responses, and angiogenesis, showing superior analgesic efficacy over vandetanib.
- In a stump neuroma model, GelMA-MAVP MPs normalized the microenvironment by inhibiting neovascularization, M1 macrophage polarization, and fibrotic scar formation.
- GelMA-MAVP MPs indirectly downregulated pain-related proteins (TRPA1/CGRP) in dorsal root ganglia and suppressed spinal microglial activation.
- The study presents a safe vascular-targeted strategy for nerve end interface self-resolution and neuropathic pain prevention.