ROS-scavenging and immunomodulatory MXene-MnO₂ hydrogel nerve conduit for peripheral nerve regeneration

A nerve guidance conduit (NGC) based on MXene-MnO₂ hydrogel is developed for the regeneration of peripheral nerves. • The NGC possesses the dual advantages for promoting Schwann cell proliferation and alleviating chronic inflammation. • The NGC can actively regulate the neural regeneration microenvironment and promote angiogenesis. • The NGC can promote neurofilament formation, remyelination and prevent muscle atrophy. Peripheral nerve regeneration remains a major challenge in clinical due to persistent inflammatory microenvironments and oxidative stress that impede functional recovery. In this study, we designed a bio-responsive nerve guidance conduit (NGC) based on a MXene-MnO₂ nanocomposite hydrogel that actively orchestrates the regenerative microenvironment through material-mediated biological crosstalk. Unlike conventional passive conduits, our system leverages the unique properties of two-dimensional MXene to enhance Schwann cell proliferation, while MnO₂ nanoparticles act as catalytic anti-oxidative modules that continuously neutralize ROS and resolve chronic inflammation. This dynamic intervention promotes a timely immune transition to shift macrophages from M1 to M2 phenotype, which facilitates angiogenesis within the injury site. In vivo tests further revealed that the treatment group not only exhibited increased neurofilament number and reduced muscle atrophy but also showed significantly enhanced remyelination. The modular design and catalytic microenvironment-regulation strategy represent a new direction in neural interface engineering. This work provides a scalable and effective platform for advanced neural repair applications and material-guided immunomodulation in regenerative medicine. Illustration of nerve regeneration promoted by MXene-MnO₂ nanocomposite hydrogel NGCs via scavenging ROS and facilitating macrophage polarization towards the M2 phenotype. Download: Download high-res image (265KB) Download: Download full-size image