title: Effect of controlled co-delivery of synergistic neurotrophic factors on early nerve regeneration in rats.
abstract: Present interventions to repair severed peripheral nerves provide slow and poor early axonal regeneration, which may cause unsatisfactory functional reinnervation. To improve early axonal regeneration in a 10 mm rat sciatic nerve gap model, we developed collagen nerve conduits loaded with the synergistically acting glial cell line-derived neurotrophic factor (GDNF) and nerve growth factor (NGF). For controlling the concomitant GDNF and NGF release, the collagen tubes were cross-linked by a dehydro-thermal treatment (110 degrees C; 20 mbar; 5 days) prior to impregnating the tubes with GDNF and NGF and by coating drug-loaded tubes with layers of poly(lactide-co-glycolide). The conduits made of cross-linked collagen released low initial amounts of GDNF and NGF (2% of both during first 3 days) and enhanced significantly the early (2 weeks) nerve regeneration in terms of axonal outgrowth and Schwann cell migration in a 10 mm rat sciatic nerve gap model, as compared to the conduits made of non-cross-linked collagen releasing higher initial amounts of GDNF and NGF (12-16% within 3 days), or those releasing GDNF alone. The enhancement of early axonal regeneration using controlled co-delivery of multiple synergistic neurotrophic factors is an important requisite for eventually establishing functional connections with the target organ.
authors.affiliation: Institute of Pharmaceutical Sciences, ETH Zurich, 8093 Zurich, Switzerland.
authors.forename: Srinivas
authors.initials: S
authors.lastname: Madduri
authors.forename: Pietro
authors.initials: P
authors.lastname: di Summa
authors.forename: Michaël
authors.initials: M
authors.lastname: Papaloïzos
authors.forename: Daniel
authors.initials: D
authors.lastname: Kalbermatten
authors.forename: Bruno
authors.initials: B
authors.lastname: Gander
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D003094:Collagen / Q000737:chemistry*; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000008:administration & dosage* / Q000627:therapeutic use; D020007:Implants, Experimental; D008297:Male; D020932:Nerve Growth Factor / Q000008:administration & dosage* / Q000627:therapeutic use; D009416:Nerve Regeneration / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure
chemical_list: D001672:Biocompatible Materials; D051100:Glial Cell Line-Derived Neurotrophic Factor; D003094:Collagen; D020932:Nerve Growth Factor