ROS filter coating scaffold protects 3D mesenchymal stem cell spheroids for dual-phase treatment of spinal cord injury

Implanting mesenchymal stem cells (MSCs) has offered a great promise in spinal cord injury (SCI) repair. However, the harsh environment accompanied with excessive ROS following SCI seriously threatens MSC survival and compromises its efficacy. Additionally, the intricate pathology distinguished as the acute phase and chronic phase makes MSC therapeutics alone difficult to alleviate severe inflammation and promote functional recovery simultaneously. Despite scaffold systems for local stem cell delivery being extensively explored, dual-phase management for SCI using one protective scaffold system has rarely been reported. Herein, a composite scaffold system (RF-pGel-MS), which consisted of an outer ROS filter (RF) and an inner porous GelMA hydrogel (pGel) harbored with MSC spheroids (MSs), was designed for SCI repair. Specifically, RF rapidly scavenged ROS, protecting the MS from peroxidation damage in the acute phase. MS constructed via 3D culture of MSCs presented enhanced paracrine effects, which remarkably facilitated neuron repair and functional recovery in the chronic phase. The dual-phase therapeutic efficacy of RF-pGel-MS led to significant locomotor and electrophysiology recovery in the SCI rats. Hence, the currently proposed strategy using RF-pGel-MS is efficient for ROS scavenging and boosting the stem cell therapeutics, which is insightful for the SCI treatment.