An injectable responsive exosome-releasing hydrogel based on sodium alginate restores motor and bladder function by alleviating the injury microenvironment and facilitating distal nerve repair

In the early stage of spinal cord injury (SCI), excessive reactive oxygen species (ROS) accumulate at the injury site to establish a microenvironment favoring complex secondary injuries, including cavity formation, and impacting the distal lumbosacral spinal cord. Currently, no definitive clinical treatment is available for SCI. Here, we created an responsive and injectable hydrogel composite (GEL-EXO) by modifying and cross-linking biological macromolecules sodium alginate (SA) and gelatin in the form of embedded exosomes. This GEL-EXO composite integrated the bioactivity of exosomes with the gap-filling function of hydrogels. Our experiments demonstrated that the composite could simultaneously repair spinal cord tissues at the injury site and the distal lumbosacral region, thereby restoring motor function and reinitiating bladder function. This therapeutic strategy may promise a brand-new holistic intervention for SCI. • An injectable GEL-EXO composite for responsive exosome releasing is constructed. • The GEL-EXO composite mitigates the injury microenvironment and promotes nerve recovery. • Bladder function is restored through repairing the distal spinal cord segment.