Cryogel scaffolds for localised delivery of lipopolysaccharide in organotypic spinal cord slice cultures: A novel ex vivo model of neuroinflammation.

Spinal cord injury (SCI) is a devastating condition for which no curative therapy is currently available. The pathology of SCI is underscored by an inflammatory lesion at the site of injury that exacerbates damage and impedes recovery. Immunomodulation is a promising strategy for SCI repair and thus there is enhanced focus on identifying and testing novel immunotherapeutics. Efficient preclinical models are required for screening new therapies, and ex vivo models can reduce the overall cost and animal numbers required for this process. Organotypic spinal cord slices offer a promising ex vivo platform for modelling spinal cord pathologies as they retain the in vivo tissue architecture with the benefit of a controlled culture environment. Neuroinflammation can be induced in organotypic spinal cord slices by adding inflammatory agents to the culture system, however this results in global inflammation and lacks the heterogeneity of a focal lesion surrounded by spared tissue that is observed in vivo. To improve this model, we have applied previously characterised macroporous cryogels for localised delivery of lipopolysaccharide (LPS) in organotypic spinal cord slices. Placement of LPS-loaded cryogels adjacent to spinal cord slices increases the expression of proinflammatory CD86 in Iba-1(+) microglia/macrophages and decreases the expression of myelin basic protein at the lesion site. These effects are not observed distal to the cryogel, indicating the formation of a focal inflammatory lesion. These effects can be reversed through treatment with the immunomodulatory cytokine interleukin(IL)-13. This novel model of neuroinflammation provides an innovative platform for screening potential immunotherapeutics and improving the efficiency of future preclinical SCI studies.