A Multifunctional Nb2C MXene-based hydrogel supports mesenchymal stem cell therapy for subacute spinal cord injury

Mesenchymal stem cell (MSC) therapy is a promising strategy for spinal cord injury (SCI), but its efficacy is limited by poor cell retention and impaired function within the inflammatory and oxidative lesion microenvironment. Here, we developed an injectable and tissue-adhesive HAFN hydrogel incorporating PDA-modified Nb₂C MXene nanosheets as a local platform for MSC delivery after SCI. HAFN exhibited favorable injectability, tissue adhesion, electrical conductivity, and reactive oxygen species-scavenging activity. In vitro, HAFN protected MSCs against oxidative stress, while HAFN-supported MSC treatment attenuated macrophage inflammatory responses and improved neural cell survival and migration. HAFN also supported neural-associated differentiation of MSCs in vitro. In a rat SCI model, treatment was administered at 7 days after injury to represent a subacute intervention. MSC-encapsulated HAFN improved local MSC retention and reduced oxidative stress, inflammation, and neuronal apoptosis. These effects were accompanied by reduced astroglial accumulation and improved neural tissue preservation, axonal and synaptic remodeling, and myelin repair, ultimately leading to better locomotor recovery. Transcriptomic analysis further revealed coordinated changes in inflammatory and cell-survival programs. Collectively, these findings identify HAFN as a multifunctional platform that integrates MSC delivery, redox regulation, immune modulation, and neural tissue repair, thereby improving the retention and therapeutic performance of MSCs for subacute SCI treatment.