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

Letao Yang, Brian M. Conley, Susana R. Cerqueira, Thanapat Pongkulapa, Shenqiang Wang, Jae K. Lee, Ki Bum Lee

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article number2002578
JournalAdvanced Materials
Volume32
Issue number43
DOIs
StatePublished - Oct 1 2020

Keywords

  • biomaterials
  • inorganic–organic hybrid nanomaterials
  • nanoscaffolds
  • neural tissue engineering
  • spinal cord injury

ASJC Scopus subject areas

  • Materials Science(all)
  • Mechanics of Materials
  • Mechanical Engineering

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