Electroactive hydrogel with human umbilical cord mesenchymal stem cell–derived exosomes remodels the microenvironment of spinal cord lesion sites and rebuilds neural circuits after injury

Spinal cord injury remains a devastating condition with no curative therapies currently available. Existing treatments are largely limited to symptomatic management and fail to address the complex pathophysiological microenvironment that hinders neural regeneration. Hydrogels with appropriate conductive properties offer potential new therapeutic avenues for treating spinal cord injury and can appropriately adjust the pathological and electrophysiological microenvironment at the injury site. Exosomes secreted by human umbilical cord mesenchymal stem cells, which can cross the blood-spinal cord barrier, have effects on repairing tissue damage and promoting cell differentiation. Here, we developed a conductive hydrogel, integrating gelatin methacrylate with polyaniline and exosomes derived from human umbilical cord mesenchymal stem cells, which exhibits excellent biocompatibility, thereby facilitating neuronal repair by activating the Wnt/β-catenin signaling pathway and improving the pathological environment at the lesion site. This hydrogel can modulate the differentiation of neural stem cells into neurons and oligodendrocytes in vitro, promoting the proliferation of neural cells. In vivo, it can improve the motor and physiological functions of rats with spinal cord injury by inhibiting scar formation and promoting nerve and myelin regeneration. The novel conductive composite hydrogel, developed in the present study and capable of loading exosomes, offers a new therapeutic strategy for spinal cord injury with promising application prospects.