Effectiveness of insolubilized polyvinyl alcohol-based electrospun fibers loaded methylprednisolone by enzyme-catalyzed cross-linking in spinal cord regeneration

Abstract

Spinal cord injury (SCI) has been implicated in neural cell loss and consequently motor/sensory impairment. In this study, we propose a new formation for fibrous mat fabrication from derivatives of poly vinyl alcohol (PVA) and gelatin (Gela) through horseradish peroxidase (HRP) mediated crosslinking, which provide sustained release of methylprednisolone (MP) that can be utilized as a therapeutic approach for SCI repair. The polymeric solution of PVA/Gela conjugated with phenolic moieties (PVAPh and GelaPh, respectively) containing HRP and MP, was fed into electrospinning system, using a syringe pump. The fabricated scaffolds were characterized in vitro and were implanted into the compression SCI rat model. After 28 days, the animals were evaluated in terms of remyelination and apoptosis and underwent behavioral test. The mechanical properties, hydrophobicity, and degradation rate of PVAPh/GelaPh fibrous mat were significantly promoted compared to PVAPh samples and could provide the desired structure for sustained release of MP. The seeded cells could adhere and proliferate on composite fibers, which indicates cytocompatibility of resultant PVAPh/GelaPh fibrous mat. The results showed a significant decrease in apoptotic neurons and a remarkable increase in remyelination in SCI + PVAPh/GelaPh + MP group compared to that in other groups. The behavioral test confirmed locomotor hind limb function amelioration after treatment. MP-loaded PVAPh/GelaPh mat developed through long-term release of MP and biocompatible fabricated mat could inhibit axonal demyelination, attenuated apoptosis, and improved functional outcome, which confirmed the potential of PVAPh/GelaPh + MP nanocomposites as a bioactive scaffold for SCI regeneration.