3D-MSCs apoptotic bodies-integrated conductive hydrogel mitigates spinal cord injury via immunoregulation and alleviating neuronal pyroptosis

Spinal cord injury (SCI) is a severe condition that affects the central nervous system. Current clinical interventions are insufficient to address the profound consequences of SCI, highlighting the great need for alternative treatment options. In recent years, the use of hydrogels to locally deliver extracellular vesicles (EVs) has become a potential method for SCI therapy, conductive hydrogels can also promote SCI repair by establishing functional connections between neurons. However, increasing the bioactivity of EVs and optimizing hydrogel-based therapies remain significant challenges. In this study, MXene nanosheets endow composite hydrogels with excellent conductivity. Bone marrow mesenchymal stem cells (BMSCs) were grown in 3D suspensions to form spheroids, after which apoptosis was induced to isolate apoptotic bodies (ABs). Then 3D-ABs were incorporated into a Gelatine methacryloyl (GelMA) hydrogel containing MXene nanosheets for their sustained release in vivo. Furthermore, the composite hydrogel provides mechanical support and mimics the electrical transmission properties of neurons. After local injection into SCI mice, the composite hydrogel effectively filled the lesion cavity, promoted the reconstruction of functional neural connections, suppressed neuroinflammation and alleviated neuronal pyroptosis owing to its conductive components and apoptotic vesicles. This novel injectable composite hydrogel represents a promising therapeutic option for SCI repair.