Long-gap peripheral nerve repair through sustained release of a neurotrophic factor in nonhuman primates. 2020

Neil B Fadia, and Jacqueline M Bliley, and Gabriella A DiBernardo, and Donald J Crammond, and Benjamin K Schilling, and Wesley N Sivak, and Alexander M Spiess, and Kia M Washington, and Matthias Waldner, and Han-Tsung Liao, and Isaac B James, and Danielle M Minteer, and Casey Tompkins-Rhoades, and Adam R Cottrill, and Deok-Yeol Kim, and Riccardo Schweizer, and Debra A Bourne, and George E Panagis, and M Asher Schusterman, and Francesco M Egro, and Insiyah K Campwala, and Tyler Simpson, and Douglas J Weber, and Trent Gause, and Jack E Brooker, and Tvisha Josyula, and Astrid A Guevara, and Alexander J Repko, and Christopher M Mahoney, and Kacey G Marra
Department of Plastic Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA.

Severe injuries to peripheral nerves are challenging to repair. Standard-of-care treatment for nerve gaps >2 to 3 centimeters is autografting; however, autografting can result in neuroma formation, loss of sensory function at the donor site, and increased operative time. To address the need for a synthetic nerve conduit to treat large nerve gaps, we investigated a biodegradable poly(caprolactone) (PCL) conduit with embedded double-walled polymeric microspheres encapsulating glial cell line-derived neurotrophic factor (GDNF) capable of providing a sustained release of GDNF for >50 days in a 5-centimeter nerve defect in a rhesus macaque model. The GDNF-eluting conduit (PCL/GDNF) was compared to a median nerve autograft and a PCL conduit containing empty microspheres (PCL/Empty). Functional testing demonstrated similar functional recovery between the PCL/GDNF-treated group (75.64 ± 10.28%) and the autograft-treated group (77.49 ± 19.28%); both groups were statistically improved compared to PCL/Empty-treated group (44.95 ± 26.94%). Nerve conduction velocity 1 year after surgery was increased in the PCL/GDNF-treated macaques (31.41 ± 15.34 meters/second) compared to autograft (25.45 ± 3.96 meters/second) and PCL/Empty (12.60 ± 3.89 meters/second) treatment. Histological analyses included assessment of Schwann cell presence, myelination of axons, nerve fiber density, and g-ratio. PCL/GDNF group exhibited a statistically greater average area occupied by individual Schwann cells at the distal nerve (11.60 ± 33.01 μm2) compared to autograft (4.62 ± 3.99 μm2) and PCL/Empty (4.52 ± 5.16 μm2) treatment groups. This study demonstrates the efficacious bridging of a long peripheral nerve gap in a nonhuman primate model using an acellular, biodegradable nerve conduit.

UI MeSH Term Description Entries
D008251 Macaca A genus of the subfamily CERCOPITHECINAE, family CERCOPITHECIDAE, consisting of 16 species inhabiting forests of Africa, Asia, and the islands of Borneo, Philippines, and Celebes. Ape, Barbary,Ape, Black,Ape, Celebes,Barbary Ape,Black Ape,Celebes Ape,Macaque,Apes, Barbary,Apes, Black,Apes, Celebes,Barbary Apes,Black Apes,Celebes Apes,Macacas,Macaques
D009416 Nerve Regeneration Renewal or physiological repair of damaged nerve tissue. Nerve Tissue Regeneration,Nervous Tissue Regeneration,Neural Tissue Regeneration,Nerve Tissue Regenerations,Nervous Tissue Regenerations,Neural Tissue Regenerations,Regeneration, Nerve,Regeneration, Nerve Tissue,Regeneration, Nervous Tissue,Regeneration, Neural Tissue,Tissue Regeneration, Nerve,Tissue Regeneration, Nervous,Tissue Regeneration, Neural
D003692 Delayed-Action Preparations Dosage forms of a drug that act over a period of time by controlled-release processes or technology. Controlled Release Formulation,Controlled-Release Formulation,Controlled-Release Preparation,Delayed-Action Preparation,Depot Preparation,Depot Preparations,Extended Release Formulation,Extended Release Preparation,Prolonged-Action Preparation,Prolonged-Action Preparations,Sustained Release Formulation,Sustained-Release Preparation,Sustained-Release Preparations,Timed-Release Preparation,Timed-Release Preparations,Controlled-Release Formulations,Controlled-Release Preparations,Extended Release Formulations,Extended Release Preparations,Slow Release Formulation,Sustained Release Formulations,Controlled Release Formulations,Controlled Release Preparation,Controlled Release Preparations,Delayed Action Preparation,Delayed Action Preparations,Formulation, Controlled Release,Formulations, Controlled Release,Prolonged Action Preparation,Release Formulation, Controlled,Release Formulations, Controlled,Sustained Release Preparation,Timed Release Preparation,Timed Release Preparations
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001369 Axons Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. Axon
D012583 Schwann Cells Neuroglial cells of the peripheral nervous system which form the insulating myelin sheaths of peripheral axons. Schwann Cell,Cell, Schwann,Cells, Schwann
D051100 Glial Cell Line-Derived Neurotrophic Factor The founding member of the glial cell line-derived neurotrophic factor family. It was originally characterized as a NERVE GROWTH FACTOR promoting the survival of MIDBRAIN dopaminergic NEURONS, and it has been studied as a potential treatment for PARKINSON DISEASE. Glial Cell-Derived Neurotrophic Factor,Glial-Derived Neurotrophic Factor,GDNF,GDNF Growth Factor,Glial Cell-Line Derived Neurotrophic Factor,Factor, Glial-Derived Neurotrophic,Glial Cell Derived Neurotrophic Factor,Glial Cell Line Derived Neurotrophic Factor,Glial Derived Neurotrophic Factor,Growth Factor, GDNF,Neurotrophic Factor, Glial-Derived

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