Effect of controlled co-delivery of synergistic neurotrophic factors on early nerve regeneration in rats.
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.
Madduri
Srinivas
S
Institute of Pharmaceutical Sciences, ETH Zurich, 8093 Zurich, Switzerland.
di Summa
Pietro
P
Papaloïzos
Michaël
M
Kalbermatten
Daniel
D
Gander
Bruno
B
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
D001672:Biocompatible Materials; D051100:Glial Cell Line-Derived Neurotrophic Factor; D003094:Collagen; D020932:Nerve Growth Factor