title: Peripheral Nerve Regeneration Through Hydrogel-Enriched Chitosan Conduits Containing Engineered Schwann Cells for Drug Delivery.
abstract: Critical length nerve defects in the rat sciatic nerve model were reconstructed with chitosan nerve guides filled with Schwann cells (SCs) containing hydrogel. The transplanted SCs were naive or had been genetically modified to overexpress neurotrophic factors, thus providing a cellular neurotrophic factor delivery system. Prior to the assessment in vivo, in vitro studies evaluating the properties of engineered SCs overexpressing glial cell line-derived neurotrophic factor (GDNF) or fibroblast growth factor 2 (FGF-2(18kDa)) demonstrated their neurite outgrowth inductive bioactivity for sympathetic PC-12 cells as well as for dissociated dorsal root ganglion cell drop cultures. SCs within NVR-hydrogel, which is mainly composed of hyaluronic acid and laminin, were delivered into the lumen of chitosan hollow conduits with a 5% degree of acetylation. The viability and neurotrophic factor production by engineered SCs within NVR-Gel inside the chitosan nerve guides was further demonstrated in vitro. In vivo we studied the outcome of peripheral nerve regeneration after reconstruction of 15-mm nerve gaps with either chitosan/NVR-Gel/SCs composite nerve guides or autologous nerve grafts (ANGs). While ANGs did guarantee for functional sensory and motor regeneration in 100% of the animals, delivery of NVR-Gel into the chitosan nerve guides obviously impaired sufficient axonal outgrowth. This obstacle was overcome to a remarkable extent when the NVR-Gel was enriched with FGF-2(18kDa) overexpressing SCs.
authors: Institute of Neuroanatomy, Hannover Medical School, Hannover, Lower-Saxony, Germany.
authors: Cora
authors: C
authors: Meyer
authors: Sandra
authors: S
authors: Wrobel
authors: Stefania
authors: S
authors: Raimondo
authors: Shimon
authors: S
authors: Rochkind
authors: Claudia
authors: C
authors: Heimann
authors: Abraham
authors: A
authors: Shahar
authors: Ofra
authors: O
authors: Ziv-Polat
authors: Stefano
authors: S
authors: Geuna
authors: Claudia
authors: C
authors: Grothe
authors: Kirsten
authors: K
authors: Haastert-Talini
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000494:pharmacology*; D016503:Drug Delivery Systems; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000378:metabolism; D005818:Genetic Engineering; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000494:pharmacology*; D007249:Inflammation / Q000473:pathology; D009043:Motor Activity / Q000187:drug effects; D009186:Myelin Sheath / Q000378:metabolism; D009416:Nerve Regeneration / Q000187:drug effects*; D009431:Neural Conduction / Q000187:drug effects; D016501:Neurites / Q000187:drug effects / Q000378:metabolism; D016716:PC12 Cells; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000187:drug effects; D012583:Schwann Cells / Q000187:drug effects / Q000378:metabolism*; D012584:Sciatic Nerve / Q000187:drug effects / Q000503:physiopathology* / Q000637:transplantation; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*; D014182:Transplantation, Autologous
chemical_list: D016222:Fibroblast Growth Factor 2; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D048271:Chitosan