TY - JOUR
T1 - Long-gap peripheral nerve repair through sustained release of a neurotrophic factor in nonhuman primates
AU - Fadia, Neil B.
AU - Bliley, Jacqueline M.
AU - DiBernardo, Gabriella A.
AU - Crammond, Donald J.
AU - Schilling, Benjamin K.
AU - Sivak, Wesley N.
AU - Spiess, Alexander M.
AU - Washington, Kia M.
AU - Waldner, Matthias
AU - Liao, Han Tsung
AU - James, Isaac B.
AU - Minteer, Danielle M.
AU - Tompkins-Rhoades, Casey
AU - Cottrill, Adam R.
AU - Kim, Deok Yeol
AU - Schweizer, Riccardo
AU - Bourne, Debra A.
AU - Panagis, George E.
AU - Asher Schusterman, M.
AU - Egro, Francesco M.
AU - Campwala, Insiyah K.
AU - Simpson, Tyler
AU - Weber, Douglas J.
AU - Gause, Trent
AU - Brooker, Jack E.
AU - Josyula, Tvisha
AU - Guevara, Astrid A.
AU - Repko, Alexander J.
AU - Mahoney, Christopher M.
AU - Marra, Kacey G.
N1 - Publisher Copyright:
Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works
PY - 2020/1/22
Y1 - 2020/1/22
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=85078275705&partnerID=8YFLogxK
U2 - 10.1126/scitranslmed.aav7753
DO - 10.1126/scitranslmed.aav7753
M3 - Article
C2 - 31969488
AN - SCOPUS:85078275705
SN - 1946-6234
VL - 12
JO - Science translational medicine
JF - Science translational medicine
IS - 527
M1 - eaav7753
ER -