The role of aligned polymer fiber-based constructs in the bridging of long peripheral nerve gaps

Abstract Peripheral nerve regeneration across long nerve gaps is clinically challenging. Autografts, the standard of therapy, are limited by availability and other complications. Here, using rigorous anatomical and functional measures, we report that aligned polymer fiber-based constructs present to...

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Bibliographic Details
Published in:Biomaterials 2008-07, Vol.29 (21), p.3117-3127
Main Authors: Kim, Young-tae, Haftel, Valerie K, Kumar, Satish, Bellamkonda, Ravi V
Format: Article
Language:English
Subjects:
Advanced Basic Science
Animals
Biocompatible Materials - chemistry
Biocompatible Materials - pharmacology
Cell migration
Dentistry
Immunohistochemistry
Laminin - analysis
Male
Muscle, Skeletal - chemistry
Muscle, Skeletal - drug effects
Muscle, Skeletal - innervation
Nerve regeneration
Nerve Regeneration - drug effects
Neurites - drug effects
Neuromuscular Junction - drug effects
Neuromuscular Junction - physiology
Peripheral Nerves - cytology
Peripheral Nerves - physiology
Polymers - chemistry
Polymers - pharmacology
Rats
S100 Proteins - analysis
Schwann Cells - cytology
Schwann Cells - drug effects
Tissue Engineering - methods
Topographical guidance
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Summary:Abstract Peripheral nerve regeneration across long nerve gaps is clinically challenging. Autografts, the standard of therapy, are limited by availability and other complications. Here, using rigorous anatomical and functional measures, we report that aligned polymer fiber-based constructs present topographical cues that facilitate the regeneration of peripheral nerves across long nerve gaps. Significantly, aligned but not randomly oriented fibers elicit regeneration, establishing that topographical cues can influence endogenous nerve repair mechanisms in the absence of exogenous growth promoting proteins. Axons regenerated across a 17 mm nerve gap, reinnervated muscles, and reformed neuromuscular junctions. Electrophysiological and behavioral analyses revealed that aligned but not randomly oriented constructs facilitated both sensory and motor nerve regeneration, significantly improved functional outcomes. Additionally, a quantitative comparison of DRG outgrowth in vitro and nerve regeneration in vivo on aligned and randomly oriented fiber films clearly demonstrated the significant role of sub-micron scale topographical cues in stimulating endogenous nerve repair mechanisms.
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2008.03.042