A Physicochemically Optimized and Neuroconductive Biphasic Nerve Guidance Conduit for Peripheral Nerve Repair

Clinically available hollow nerve guidance conduits (NGCs) have had limited success in treating large peripheral nerve injuries. This study aims to develop a biphasic NGC combining a physicochemically optimized collagen outer conduit to bridge the transected nerve, and a neuroconductive hyaluronic a...

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Bibliographic Details
Published in:Advanced healthcare materials 2017-12, Vol.6 (24), p.n/a
Main Authors: Ryan, Alan J., Lackington, William A., Hibbitts, Alan J., Matheson, Austyn, Alekseeva, Tijna, Stejskalova, Anna, Roche, Phoebe, O'Brien, Fergal J.
Format: Article
Language:English
Subjects:
aligned microarchitecture
Biological activity
biomimicry
Cell adhesion
Cells (biology)
Collagen
Computer architecture
Crosslinking
Defects
Dorsal root ganglia
Freeze drying
Ganglia
Gliogenesis
Hyaluronic acid
Injury prevention
Laminin
natural polymers
Nerve guides
neural engineering
Neural stem cells
Neurogenesis
Optimization
peripheral nerve
Permeability
Regeneration
Schwann cells
Stiffness
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Summary:Clinically available hollow nerve guidance conduits (NGCs) have had limited success in treating large peripheral nerve injuries. This study aims to develop a biphasic NGC combining a physicochemically optimized collagen outer conduit to bridge the transected nerve, and a neuroconductive hyaluronic acid‐based luminal filler to support regeneration. The outer conduit is mechanically optimized by manipulating crosslinking and collagen density, allowing the engineering of a high wall permeability to mitigate the risk of neuroma formation, while also maintaining physiologically relevant stiffness and enzymatic degradation tuned to coincide with regeneration rates. Freeze‐drying is used to seamlessly integrate the luminal filler into the conduit, creating a longitudinally aligned pore microarchitecture. The luminal stiffness is modulated to support Schwann cells, with laminin incorporation further enhancing bioactivity by improving cell attachment and metabolic activity. Additionally, this biphasic NGC is shown to support neurogenesis and gliogenesis of neural progenitor cells and axonal outgrowth from dorsal root ganglia. These findings highlight the paradigm that a successful NGC requires the concerted optimization of both a mechanical support phase capable of bridging a nerve defect and a neuroconductive phase with an architecture capable of supporting both Schwann cells and neurons in order to achieve functional regenerative outcome. A biphasic nerve guidance conduit is fabricated by combining a physicochemically optimized collagen‐based outer conduit with a neuroconductive hyaluronic acid‐laminin luminal filler that has a longitudinally aligned porous microarchitecture capable of supporting dorsal root ganglia axonal outgrowth, neurogenesis & gliogenesis, and Schwann cell growth.
ISSN:2192-2640
2192-2659
DOI:10.1002/adhm.201700954