Effective Modulation of CNS Inhibitory Microenvironment using Bio-inspired Hybrid Nanoscaffold-based Therapeutic Interventions

• Published in: Advanced materials (Weinheim) 2020-09, Vol.32 (43), p.e2002578-e2002578
• Main Authors: Yang, Letao, Conley, Brian M., Cerqueira, Susana R., Pongkulapa, Thanapat, Wang, Shenqiang, Lee, Jae K., Lee, Ki-Bum
• Format: Article
• Language: English
• ISSN: 0935-9648; 1521-4095
• DOI: 10.1002/adma.202002578

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, we developed a viscous interfacial self-assembly approach to generate a bio-inspired hybrid three dimensional (3D) porous nanoscaffold platform for delivering anti-inflammatory molecules and establishing a favorable 3D-ECM environment for the effective suppression of the neuroinhibitory microenvironment. By tailoring the structural and biochemical properties of the 3D porous nanoscaffold, we demonstrate enhanced axonal growth from the dual-targeting therapeutic strategy in a human induced pluripotent stem cell (hiPSC)-based in vitro model of neuroinflammation. 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, our developed nanobiomaterial-based therapeutic intervention may pave a new road for treating CNS injuries. Current biomaterials-based treatment of CNS injuries has been hampered by the resulting neuroinhibitory microenvironment. By targeting two critical neuroinhibitory factors in a single platform, a biomimetic 3D porous hybrid nanoscaffold is created by developing viscous interfacial self-assembly. The nanoscaffold-based achieved functional recovery through reducing neuroinflammation and fibrotic scarring, thereby paving a new road for the biomaterials-based treatment of CNS injuries.