title: Short- and long-term peripheral nerve regeneration using a poly-lactic-co-glycolic-acid scaffold containing nerve growth factor and glial cell line-derived neurotrophic factor releasing microspheres.
abstract: Addition of neural growth factors to bioengineered scaffolds may improve peripheral nerve regeneration. The aim of this study is to evaluate the short- and long term effect of microsphere delivered nerve growth factor (NGF) and glial cell derived neurotrophic factor (GDNF) in the 10 mm rat sciatic nerve gap. Eighty-four rats were assigned to seven groups (n = 6) at two endpoints (6 and 16 weeks): saline, saline NGF, saline NGF-microspheres, saline GDNF, saline GDNF-microspheres, saline blank microspheres, and autologous nerve graft. Total fascicular area and total number of myelinated fibers at mid-tube increased in all conduit groups between 6 and 16 weeks. Autologous, saline NGF-microsphere and saline GDNF-microsphere groups reached maximal histomorphometric values by 6 weeks (p < 0.05). Compound muscle action potentials returned after 6 weeks for the autologous graft and continued to increase to a level of 3.6 ± 1.9 mV at endpoint. No significant differences were found between study groups as measured by ankle angle. These experiments show an initial beneficial effect of incorporation of NGF- or GDNF-microspheres in a PLGA 85/15 nerve conduit, since histomorphometric values reached their maximum by 6 weeks compared to control groups. These results do not yet extrapolate into improved electrophysiological or functional improvement.
authors.affiliation: Department of Neurology and Molecular Neuroscience, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
authors.forename: Ralph
authors.initials: R
authors.lastname: de Boer
authors.forename: Andreas
authors.initials: A
authors.lastname: Borntraeger
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Knight
authors.forename: Marie-Noëlle
authors.initials: MN
authors.lastname: Hébert-Blouin
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Spinner
authors.forename: Martijn J A
authors.initials: MJ
authors.lastname: Malessy
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Yaszemski
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Windebank
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000494:pharmacology*; D019344:Lactic Acid / Q000737:chemistry*; D008863:Microspheres; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology; D009068:Movement / Q000187:drug effects; D009132:Muscles / Q000187:drug effects / Q000502:physiology; D009416:Nerve Regeneration / Q000187:drug effects*; D010525:Peripheral Nerves / Q000187:drug effects* / Q000502:physiology*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D051100:Glial Cell Line-Derived Neurotrophic Factor; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid