Sustained release of hydrogen sulfide from anisotropic ferrofluid hydrogel for the repair of spinal cord injury.

Abstract

Spinal cord injury (SCI) results in massive neuronal death, axonal disruption, and cascading inflammatory response, which causes further damage to impaired neurons. The survived neurons with damaged function fail to form effective neuronal circuits. It is mainly caused by the neuroinflammatory microenvironment at injury sites and regenerated axons without guidance. To address this challenge, a ferrofluid hydrogel (FFH) was prepared with Ferric tetrasulfide (Fe₃S₄), carboxymethyl chitosan, and gold. Its internal structural particles can be oriented in a magnetic field to acquire anisotropy. Moreover, Fe₃S₄ can release hydrogen sulfide (H₂S) with anti-inflammatory effects under acidic conditions. Regarding <i>in vitro</i> experiments, 0.01g/ml Fe₃S₄ FFH significantly reduced the inflammatory factors produced by LPS-induced BV2 cells. Oriented and longer axons of the induced neural stem cells loaded on anisotropic FFH were observed. <i>In vivo</i> experiments showed that FFH reduced the activated microglia/macrophage and the expression of pro-inflammatory factors in SCI rats through the NF-κB pathway. Moreover, it significantly promoted directional axonal regrowth and functional recovery after SCI. Given the critical role of inhibition of neuroinflammation and directional axonal growth, anisotropic Fe₃S₄ FFH is a promising alternative for the treatment of SCI.