The role of aligned polymer fiber-based constructs in the bridging of long peripheral nerve gaps.
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.
Kim
Young-Tae
YT
Neurological Biomaterials and Therapeutics, Laboratory for Neuroengineering, Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, United States.
Haftel
Valerie K
VK
Kumar
Satish
S
Bellamkonda
Ravi V
RV
D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000494:pharmacology; D007150:Immunohistochemistry; D007797:Laminin / Q000032:analysis; D008297:Male; D018482:Muscle, Skeletal / Q000737:chemistry / Q000187:drug effects / Q000294:innervation; D009416:Nerve Regeneration / Q000187:drug effects*; D016501:Neurites / Q000187:drug effects; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology; D010525:Peripheral Nerves / Q000166:cytology* / Q000502:physiology*; D011108:Polymers / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D009418:S100 Proteins / Q000032:analysis; D012583:Schwann Cells / Q000166:cytology / Q000187:drug effects; D023822:Tissue Engineering / Q000379:methods
D001672:Biocompatible Materials; D007797:Laminin; D011108:Polymers; D009418:S100 Proteins