Engineered nerve guide conduit enhances peripheral nerve regeneration by modulating the microenvironment through macrophage-triggered cascade reactions.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 40809082.
- Also identified by DOI 10.1016/j.bioactmat.2025.04.033 and PMC identifier 12348796.
- Licence recorded as CC BY-NC-ND.
- Because redistribution is not established, this page shows the abstract only. Follow the links below for the full text.
Abstract
Nerve regeneration after peripheral nerve injury (PNI) depends on exogenous and endogenous pro-healing signals in the microenvironment. Maintaining immune system homeostasis and remodeling the regenerative microenvironment are crucial prerequisites for promoting nerve regeneration. Here, a double-layer PSM/Gel-SC(IL-4) nerve guide conduit was fabricated by photocrosslinking poly (ethylene glycol) diacrylate (PEGDA) and methacrylic acid-sodium alginate (SAMA) hydrogel as the outer layer, with GelMA encapsulating IL-4 overexpressing Schwann cells as the inner layer. PSM/Gel-SC(IL-4) conduit enabled the sustained release of IL-4, inducing pro-healing macrophages polarization through JAK1/STAT6 pathway <i>in vitro</i>. The polarized macrophages further triggered the cellular cascade reactions, enhancing the pro-healing characteristics of endothelial cells and Schwann cells. In addition, PSM/Gel-SC(IL-4) conduit significantly promoted functional recovery and nerve regeneration in 12-mm rat sciatic nerve defect model, induced pro-healing macrophage polarization at the early stage and accelerated angiogenesis and myelination at the nerve regeneration stage. This study developed a novel immunomodulatory strategy to remodel the regenerative microenvironment, and explored the underlying cellular and molecular mechanism, demonstrating considerable therapeutic potential for long-distance nerve defect.