Journal
ADVANCED MATERIALS
Volume 32, Issue 43, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adma.202002578
Keywords
biomaterials; inorganic-organic hybrid nanomaterials; nanoscaffolds; neural tissue engineering; spinal cord injury
Categories
Funding
- NSF [CBET-1803517]
- New Jersey Commission on Spinal Cord Research [CSCR17IRG010, CSCR16ERG019]
- NINDS [R01NS081040]
- NIH [S10OD023579, 1R01DC016612, 3R01DC016612-01S1, 5R01DC016612-02S1, R21AR071101]
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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.
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