Effective Modulation of CNS Inhibitory Microenvironment using Bioinspired Hybrid-Nanoscaffold-Based Therapeutic Interventions

Adv Mater. 2020 Oct;32(43):e2002578. doi: 10.1002/adma.202002578. Epub 2020 Sep 6.


Central nervous system (CNS) injuries are often debilitating, and most currently have no cure. This is due to the formation of a neuroinhibitory microenvironment at injury sites, which includes neuroinflammatory signaling and non-permissive extracellular matrix (ECM) components. To address this challenge, a viscous interfacial self-assembly approach, to generate a bioinspired hybrid 3D porous nanoscaffold platform for delivering anti-inflammatory molecules and establish a favorable 3D-ECM environment for the effective suppression of the neuroinhibitory microenvironment, is developed. By tailoring the structural and biochemical properties of the 3D porous nanoscaffold, enhanced axonal growth from the dual-targeting therapeutic strategy in a human induced pluripotent stem cell (hiPSC)-based in vitro model of neuroinflammation is demonstrated. Moreover, nanoscaffold-based approaches promote significant axonal growth and functional recovery in vivo in a spinal cord injury model through a unique mechanism of anti-inflammation-based fibrotic scar reduction. Given the critical role of neuroinflammation and ECM microenvironments in neuroinhibitory signaling, the developed nanobiomaterial-based therapeutic intervention may pave a new road for treating CNS injuries.

Keywords: biomaterials; inorganic-organic hybrid nanomaterials; nanoscaffolds; neural tissue engineering; spinal cord injury.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology
  • Axons / drug effects
  • Axons / metabolism
  • Biomimetic Materials / chemistry*
  • Biomimetic Materials / pharmacology*
  • Biomimetic Materials / therapeutic use
  • Cellular Microenvironment / drug effects*
  • Central Nervous System / drug effects*
  • Drug Carriers / chemistry*
  • Drug Carriers / pharmacology*
  • Drug Carriers / therapeutic use
  • Extracellular Matrix / drug effects
  • Extracellular Matrix / metabolism
  • Humans
  • Induced Pluripotent Stem Cells / cytology
  • Induced Pluripotent Stem Cells / drug effects
  • Mice
  • Nanostructures / chemistry*
  • Porosity
  • Spinal Cord Injuries / drug therapy
  • Spinal Cord Injuries / pathology


  • Anti-Inflammatory Agents
  • Drug Carriers