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

Abstract 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 Zn 2+ and ChABC in a pH-responsive manner to facilitate in situ SCI repair. In vitro , Z@C-MN can down-regulate the inflammatory response of macrophages, promote axon extension and the differentiation of neural stem cells into neurons. In vivo , Z@C-MN reduced the inflammatory microenvironment after injury model and promoted angiogenesis in a rat SCI. In addition, it activated axonal regeneration and supported neurogenesis by inhibiting nerve scar tissue formation and regulating the transformation of CD4 + T cells. 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.