Long-gap peripheral nerve repair through sustained release of a neurotrophic factor in nonhuman primates
| Autor: | Neil B. Fadia, Gabriella DiBernardo, Jack E. Brooker, Alexander J. Repko, Christopher Mahoney, Donald J. Crammond, Douglas J. Weber, Benjamin K. Schilling, Danielle M. Minteer, Debra A. Bourne, Casey Tompkins-Rhoades, Astrid A. Guevara, George E. Panagis, Wesley N. Sivak, Isaac B. James, Han Tsung Liao, Kia M. Washington, Adam R. Cottrill, Matthias Waldner, Jacqueline M. Bliley, Francesco M. Egro, Riccardo Schweizer, Insiyah Campwala, Deok‐Yeol Kim, Trent M. Gause, M. Asher Schusterman, Kacey G. Marra, Alexander M. Spiess, Tyler Simpson, Tvisha Josyula |
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| Přispěvatelé: | University of Zurich, Marra, Kacey |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Nerve guidance conduit Urology Schwann cell 610 Medicine & health Nerve fiber 2700 General Medicine Nerve conduction velocity 03 medical and health sciences 0302 clinical medicine Neurotrophic factors medicine Glial cell line-derived neurotrophic factor Animals Glial Cell Line-Derived Neurotrophic Factor 10266 Clinic for Reconstructive Surgery biology business.industry General Medicine musculoskeletal system Neuroma medicine.disease Axons Median nerve Nerve Regeneration 030104 developmental biology medicine.anatomical_structure nervous system Delayed-Action Preparations biology.protein Macaca Schwann Cells business 030217 neurology & neurosurgery |
| Zdroj: | Science Translational Medicine. 12 |
| ISSN: | 1946-6242 1946-6234 |
| DOI: | 10.1126/scitranslmed.aav7753 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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