Multi-time-point controlled-release methylprednisolone composite scaffolds based on clinical benchmarking for promoting spinal cord injury repair.

The inflammatory response after spinal cord injury (SCI) significantly impacts the structural and functional recovery of the nervous system. The current clinical anti-inflammatory treatment regimen, high-dose, staged intravenous administration of methylprednisolone (MP), is considered effective, but has been questioned due to the side effects associated with high-dose drug use. In this work, we designed an implantable biphasic composite scaffold (MP-CS/MP-PCL) based on clinical benchmarking for localized and programmed delivery of MP for SCI repair, which could simulate a 15-day clinical treatment regimen but significantly reduces the usage of MP. In vitro experiments demonstrate that the composite scaffold exhibits outstanding stability, biocompatibility, and potent anti-inflammatory effects. It significantly suppresses the secretion of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), and inhibits the polarization of immune cells toward the pro-inflammatory M1 phenotype. In vivo studies indicate that the composite scaffold effectively suppresses the prolonged release of pro-inflammatory cytokines (TNF-α and IL-1β), inhibits glial scar formation, repairs damaged spinal cord tissue, and finally promoting the recovery of hindlimb motor function. The MP-CS/MP-PCL composite scaffold offers a safe, effective, and potentially alternative strategy to traditional clinical high-dose intravenous therapy.