A MnO₂ Nanoparticle-Dotted Hydrogel Promotes Spinal Cord Repair <i>via</i> Regulating Reactive Oxygen Species Microenvironment and Synergizing with Mesenchymal Stem Cells

Abstract

Spinal cord injury (SCI) is one of the most debilitating injuries, and transplantation of stem cells in a scaffold is a promising strategy for treatment. However, stem cell treatment of SCI has been severely impaired by the increased generation of reactive oxygen species in the lesion microenvironment, which can lead to a high level of stem cell death and dysfunction. Herein, a MnO₂ nanoparticle (NP)-dotted hydrogel is prepared through dispersion of MnO₂ NPs in a PPFLMLLKGSTR peptide modified hyaluronic acid hydrogel. The peptide-modified hydrogel enables the adhesive growth of mesenchymal stem cells (MSCs) and nerve tissue bridging. The MnO₂ NPs alleviate the oxidative environment, thereby effectively improving the viability of MSCs. Transplantation of MSCs in the multifunctional gel generates a significant motor function restoration on a long-span rat spinal cord transection model and induces an <i>in vivo</i> integration as well as neural differentiation of the implanted MSCs, leading to a highly efficient regeneration of central nervous spinal cord tissue. Therefore, the MnO₂ NP-dotted hydrogel represents a promising strategy for stem-cell-based therapies of central nervous system diseases through the comprehensive regulation of pathological microenvironment complications.