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Improved functional recovery in rat spinal cord injury induced by a drug combination administered via an implantable polymeric delivery system.

Spinal cord injury (SCI) is an incurable condition, in which a cascade of cellular and molecular events triggered by inflammation and excitotoxicity impairs endogenous regeneration, namely remyelination and axonal outgrowth. We designed a treatment solution based on an implantable biomaterial (electrospun PLLA) loaded with ibuprofen and triiodothyronine (T3) to counteract inflammation, thus improving endogenous regeneration. In vivo efficacy was tested by implanting the drug-loaded-PLLA in the rat model of T8 contusion SCI. We observed the expected recovery of locomotion beginning on day 7. In PLLA-implanted rats (i.e. controls), the recovery stabilized at 21 days post lesion (DPL), after which no further improvement was observed. On the contrary, in PLLA+Ibu+T3 rats a further recovery and a significant treatment effect were observed, also confirmed by the gait analysis on 49DPL. Glutamate release at 24 hours and 8DPL was reduced in PLLA+Ibu+T3- compared to PLLA-implanted rats, such as the estimated lesion volume at 60DPL. The myelin and 200-neurofilament-positive area-fraction was higher in PLLA+Ibu+T3 implanted rats, where the percentage of astrocytes was significantly reduced. The implant of a PLLA electrospun scaffold loaded with ibuprofen and T3 significantly improves the endogenous regeneration, leading to an improvement of the functional locomotion outcome in the SCI.