Microgel-encapsulated tetrandrine nanoparticles promote spinal cord repair by sustaining neuroinflammation inhibition

Abstract

Traumatic spinal cord injury (SCI) initiates an intricate secondary injury cascade, characterized by persistent inflammatory responses with neurotoxic microglia and astrocyte activation. Inhibition of neuroinflammation would significantly benefit SCI treatment. Here, tetrandrine with anti-neuroinflammatory activity was delivered into the intrathecal space for SCI treatment. The tetrandrine was encapsulated in MPEG-PDLLA nanoparticles and further loaded into GelMA microgels via a fast 3D printing process based on digital light. After intrathecal injection, the drug-loaded microgels could sustain the release of tetrandrine in the intrathecal space, resulting in efficient repair of the injured spinal cord with recovery of function. Its mechanisms were associated with the modulation of neurotoxic microglia and astrocytes as well as their crosstalk. This work demonstrates a tetrandrine-loaded microgel with potential application in SCI treatment via sustained inhibition of neuroinflammation.