title: Spider silk constructs enhance axonal regeneration and remyelination in long nerve defects in sheep.
abstract: BACKGROUND
  Surgical reapposition of peripheral nerve results in some axonal regeneration and functional recovery, but the clinical outcome in long distance nerve defects is disappointing and research continues to utilize further interventional approaches to optimize functional recovery. We describe the use of nerve constructs consisting of decellularized vein grafts filled with spider silk fibers as a guiding material to bridge a 6.0 cm tibial nerve defect in adult sheep.
  
  
  RESULTS
  The nerve constructs were compared to autologous nerve grafts. Regeneration was evaluated for clinical, electrophysiological and histological outcome. Electrophysiological recordings were obtained at 6 months and 10 months post surgery in each group. Ten months later, the nerves were removed and prepared for immunostaining, electrophysiological and electron microscopy. Immunostaining for sodium channel (NaV 1.6) was used to define nodes of Ranvier on regenerated axons in combination with anti-S100 and neurofilament. Anti-S100 was used to identify Schwann cells. Axons regenerated through the constructs and were myelinated indicating migration of Schwann cells into the constructs. Nodes of Ranvier between myelin segments were observed and identified by intense sodium channel (NaV 1.6) staining on the regenerated axons. There was no significant difference in electrophysiological results between control autologous experimental and construct implantation indicating that our construct are an effective alternative to autologous nerve transplantation.
  
  
  CONCLUSIONS
  This study demonstrates that spider silk enhances Schwann cell migration, axonal regrowth and remyelination including electrophysiological recovery in a long-distance peripheral nerve gap model resulting in functional recovery. This improvement in nerve regeneration could have significant clinical implications for reconstructive nerve surgery.
authors.affiliation: Department of Plastic, Hand and Reconstructive Surgery, Hannover Medical School, Hannover, Germany. radtke.christine@mh-hannover.de
authors.forename: Christine
authors.initials: C
authors.lastname: Radtke
authors.forename: Christina
authors.initials: C
authors.lastname: Allmeling
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Waldmann
authors.forename: Kerstin
authors.initials: K
authors.lastname: Reimers
authors.forename: Kerstin
authors.initials: K
authors.lastname: Thies
authors.forename: Henning C
authors.initials: HC
authors.lastname: Schenk
authors.forename: Anja
authors.initials: A
authors.lastname: Hillmer
authors.forename: Merlin
authors.initials: M
authors.lastname: Guggenheim
authors.forename: Gudrun
authors.initials: G
authors.lastname: Brandes
authors.forename: Peter M
authors.initials: PM
authors.lastname: Vogt
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D005260:Female; D009186:Myelin Sheath / Q000378:metabolism*; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000378:metabolism; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D010525:Peripheral Nerves / Q000502:physiology / Q000601:surgery / Q000637:transplantation; D010523:Peripheral Nervous System Diseases / Q000534:rehabilitation / Q000601:surgery* / Q000628:therapy; D020127:Recovery of Function; D034561:Sheep, Domestic; D047011:Silk / Q000737:chemistry / Q000494:pharmacology*; D013112:Spiders; D013979:Tibial Nerve / Q000293:injuries / Q000502:physiology / Q000601:surgery; D054457:Tissue Scaffolds / Q000737:chemistry; D015854:Up-Regulation
chemical_list: D047011:Silk