Impeding glial scarring hyperplasia and activating axon neogenesis via immunomodulatory microneedle patch for spinal cord repair.

Immune dysregulation and scar tissue formation following traumatic spinal cord injury (SCI) result in the generation of a microenvironment that significantly inhibits nerve regeneration and functional recovery. Continuous drug delivery across the dura, with minimal damage, and modulation of this inhibitory microenvironment pose substantial challenges in SCI treatment. This study fabricated a pH-responsive immunomodulatory microneedle (MN) patch by incorporating zeolitic imidazolate framework-8 (Zif-8) nanoparticles loaded with chondroitinase ABC (ChABC) into a gelatin methacrylate (GelMA) hydrogel (Z@C-MN). As the patch progressively degraded, this system continuously released Zn2+ and ChABC in a pH-responsive manner to facilitate in situ SCI repair. In vitro, Z@C-MN can down-regulate macrophage inflammatory responses, promote axon extension, and differentiate neural stem cells into neurons. In vivo, Z@C-MN reduced the inflammatory microenvironment in an injury model and promoted angiogenesis in a rat SCI model. In addition, it promoted axonal regeneration and neurogenesis by inhibiting nerve scar formation and regulating CD4+ T cell transformation. These effects contributed to the recovery of motor and neurological functions. Thus, this drug delivery system offers a highly efficient, transdural, and continuous-release multifunctional platform for patients with SCI.