title: An engineered biocompatible drug delivery system enhances nerve regeneration after delayed repair.
abstract: Localized drug delivery strategies could greatly benefit patients with peripheral nerve injury and could be easy for surgeons to implement. We developed a local drug delivery system (DDS) using drug-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres (MS) embedded in a fibrin gel. In an in vitro study, we investigated the biocompatibility of this DDS by performing a toxicity assay in which we incubated PC-12 cells with the medium released from the DDS in vitro. In an in vivo study, this DDS was applied at the rat common peroneal (CP) nerve injury site to deliver exogenous glial cell line-derived neurotrophic factor (GDNF) to the regenerating axons after delayed nerve repair. In vitro, PC-12 cells incubated with released media samples from the DDS had similar viability to control cells cultured with normal media, demonstrating that the DDS was not toxic. In vivo, the numbers of motor and sensory neurons that regenerated their axons with empty MS treatment were the same as when there was no MS treatment. The DDS increased the numbers of regenerating motor- and sensory neurons to levels indistinguishable from those observed with immediate nerve repair. The DDS increased neuron regeneration to levels double those observed with negative control groups. This biocompatible, nontoxic, fibrin gel-based DDS enhances outcomes following severe peripheral nerve injuries.
authors.affiliation: Division of Plastic and Reconstructive Surgery, the Hospital for Sick Children, 555 University Ave, Toronto, Ontario, M5G1X8, Canada.|Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Kasra
authors.initials: K
authors.lastname: Tajdaran
authors.affiliation: Division of Plastic and Reconstructive Surgery, the Hospital for Sick Children, 555 University Ave, Toronto, Ontario, M5G1X8, Canada.|Division of Plastic and Reconstructive Surgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.|Program in Neuroscience, the Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.
authors.forename: Tessa
authors.initials: T
authors.lastname: Gordon
authors.affiliation: Division of Plastic and Reconstructive Surgery, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Mathew D
authors.initials: MD
authors.lastname: Wood
authors.affiliation: Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada.|Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Molly S
authors.initials: MS
authors.lastname: Shoichet
authors.affiliation: Division of Plastic and Reconstructive Surgery, the Hospital for Sick Children, 555 University Ave, Toronto, Ontario, M5G1X8, Canada.|Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada.|Division of Plastic and Reconstructive Surgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.|Program in Neuroscience, the Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.
authors.forename: Gregory H
authors.initials: GH
authors.lastname: Borschel
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods*; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000737:chemistry / Q000494:pharmacology; D019344:Lactic Acid / Q000737:chemistry / Q000494:pharmacology; D008863:Microspheres; D009416:Nerve Regeneration / Q000187:drug effects*; D016716:PC12 Cells; D059348:Peripheral Nerve Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011100:Polyglycolic Acid / Q000737:chemistry / Q000494:pharmacology; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats
chemical_list: D051100:Glial Cell Line-Derived Neurotrophic Factor; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: biomaterials; chronic axotomy; chronic denervation; drug delivery; glial cell line-derived neurotrophic factor; nerve injury; regenerative medicine