Bredigite-based Bioactive Nerve Guidance Conduit for Pro-healing Macrophage Polarization And Peripheral Nerve Regeneration.

Structural and functional healing of peripheral nerves damaged by trauma or chronic disease remain major clinical challenges, requiring the development of an effective nerve guidance conduit (NGC). The present study investigated a NGC fabrication strategy based on bredigite (BRT, Ca 7 MgSi 4 O 16 ) bioceramic for the treatment of peripheral nerve injury. Here, BRT bioceramic showed good biocompatibility and sustainable release of Ca 2+ , Mg 2+ and Si 4+ ions. Both BRT extracts and BRT-incorporating electrospun membranes promoted the proliferation and myelination potential of RSC96 cells, as well as accelerated vascular formation by human umbilical vein endothelial cells. Notably, BRT facilitated RAW 264.7 cell polarization to the pro-healing phenotype under LPS-induced inflammatory stimulation. More importantly, the macrophages activated by BRT in turn promoted RSC96 cell migration and remyelination. In a rat sciatic nerve defect model, improved electrophysiological performance and alleviated gastrocnemius muscle atrophy were observed at 12 weeks post-implantation. Further experiments verified that BRT-loaded NGC facilitated axonal regrowth and revascularization with high M2-like macrophage infiltration. These findings support the beneficial effects of BRT for creating a pro-healing immune microenvironment and orchestrating multicellular processes associated with functional nerve regeneration, indicating the potential of rationally engineered bioceramics as safe, effective and economical materials for peripheral nerve repair. This article is protected by copyright. All rights reserved.