title: Functional motor recovery is improved due to local placement of GDNF microspheres after delayed nerve repair.
abstract: The majority of bioengineering strategies to promote peripheral nerve regeneration after injury have focused on therapies to bridge large nerve defects while fewer therapies are being developed to treat other nerve injuries, such as nerve transection. We constructed delivery systems using fibrin gels containing either free GDNF or polylactide-glycolic acid (PLGA) microspheres with GDNF to treat delayed nerve repair, where ELISA verified GDNF release. We determined the formulation of microspheres containing GDNF that optimized nerve regeneration and functional recovery in a rat model of delayed nerve repair. Experimental groups underwent delayed nerve repair and treatment with GDNF microspheres in fibrin glue at the repair site or control treatments (empty microspheres or free GDNF without microspheres). Contractile muscle force, muscle mass, and MUNE were measured 12 weeks following treatment, where GDNF microspheres (2 weeks formulation) were superior compared to either no GDNF or short-term release of free GDNF to nerve. Nerve histology distal to the repair site demonstrated increased axon counts and fiber diameters due to GDNF microspheres (2 weeks formulation). GDNF microspheres partially reversed the deleterious effects of chronic nerve injury, and recovery was slightly favored with the 2 weeks formulation compared to the 4 weeks formulation.
authors.affiliation: Division of Plastic and Reconstructive Surgery, The Hospital for Sick Children, 555 University Ave, Toronto, Ontario, Canada M5G 1X8. matt.wood.tkd@gmail.com
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Wood
authors.forename: Tessa
authors.initials: T
authors.lastname: Gordon
authors.forename: Stephen W P
authors.initials: SW
authors.lastname: Kemp
authors.forename: Edward H
authors.initials: EH
authors.lastname: Liu
authors.forename: Howard
authors.initials: H
authors.lastname: Kim
authors.forename: Molly S
authors.initials: MS
authors.lastname: Shoichet
authors.forename: Gregory H
authors.initials: GH
authors.lastname: Borschel
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001369:Axons / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry; D005260:Female; D015718:Fibrin Tissue Adhesive / Q000737:chemistry; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000008:administration & dosage* / Q000737:chemistry*; D019344:Lactic Acid / Q000008:administration & dosage / Q000737:chemistry; D008863:Microspheres; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000187:drug effects*; D009133:Muscular Atrophy / Q000473:pathology; D009186:Myelin Sheath / Q000737:chemistry / Q000378:metabolism; D011100:Polyglycolic Acid / Q000008:administration & dosage / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects* / Q000293:injuries / Q000503:physiopathology
chemical_list: D004337:Drug Carriers; D015718:Fibrin Tissue Adhesive; D051100:Glial Cell Line-Derived Neurotrophic Factor; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid