L. Eumelanin decorated poly(lactic acid) electrospun substrates as a new strategy for spinal cord injury treatment

Spinal cord injury (SCI) is characterized by neuroinflammatory processes that are marked by an uncontrolled activation of microglia, which directly damages neurons. Natural and synthetic melanins represent an effective tool to treat neuroinflammation because they possess immunomodulatory properties. Here, the effect of eumelanin-coated poly(lactic acid) (PLA) aligned microfibers (EU@PLA) on neuroinflammation was investigated in terms of inflammatory mediators modulation. Eumelanin decorated PLA electrospun substrates were produced combining electrospinning, spin coating and solid-state polymerization processes (oxidative coupling under oxygen atmosphere). Biological response in terms of antioxidant and anti-inflammatory activity was analysed on an in vitro model of neuroinflammation [(microglial cells stimulated with lipopolysaccharide (LPS)]. Cell morphology and EU@PLA mechanism of action, in terms of toll-like receptor-4 (TLR-4) involvement were assessed. The results show that EU@PLA fibers were able to decrease reactive oxygen species, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-?B) expression and interleukin 6 (IL-6) secretion. Finally, the mechanism of action of EU@PLA in microglia was found to be dependent on the TLR-4 signaling as protein expression analysis revealed a decreased in TLR-4 production induced by LPS stimulation. Overall, our results show that EU@PLA represents an innovative and effective strategy for the control of inflammatory response in central nervous system.