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

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

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numbereaav7753
JournalScience translational medicine
Volume12
Issue number527
DOIs
StatePublished - Jan 22 2020

ASJC Scopus subject areas

  • Medicine(all)

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