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Erythropoietin-PLGA-PEG as a local treatment to promote functional recovery and neurovascular regeneration after peripheral nerve injury

BACKGROUND: Traumatic peripheral nerve injury (TPNI) is a major medical problem with no universally accepted pharmacologic treatment. We hypothesized that encapsulation of pro-angiogenic erythropoietin (EPO) in amphiphilic PLGA-PEG block copolymers could serve as a local controlled-release drug deli...

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Autores principales: Manto, Kristen M., Govindappa, Prem Kumar, Martinazzi, Brandon, Han, Aijie, Hegarty, John P., Koroneos, Zachary, Talukder, M. A. Hassan, Elfar, John C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9617443/
https://www.ncbi.nlm.nih.gov/pubmed/36307805
http://dx.doi.org/10.1186/s12951-022-01666-5
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author Manto, Kristen M.
Govindappa, Prem Kumar
Martinazzi, Brandon
Han, Aijie
Hegarty, John P.
Koroneos, Zachary
Talukder, M. A. Hassan
Elfar, John C.
author_facet Manto, Kristen M.
Govindappa, Prem Kumar
Martinazzi, Brandon
Han, Aijie
Hegarty, John P.
Koroneos, Zachary
Talukder, M. A. Hassan
Elfar, John C.
author_sort Manto, Kristen M.
collection PubMed
description BACKGROUND: Traumatic peripheral nerve injury (TPNI) is a major medical problem with no universally accepted pharmacologic treatment. We hypothesized that encapsulation of pro-angiogenic erythropoietin (EPO) in amphiphilic PLGA-PEG block copolymers could serve as a local controlled-release drug delivery system to enhance neurovascular regeneration after nerve injury. METHODS: In this study, we synthesized an EPO-PLGA-PEG block copolymer formulation. We characterized its physiochemical and release properties and examined its effects on functional recovery, neural regeneration, and blood vessel formation after sciatic nerve crush injury in mice. RESULTS: EPO-PLGA-PEG underwent solution-to-gel transition within the physiologically relevant temperature window and released stable EPO for up to 18 days. EPO-PLGA-PEG significantly enhanced sciatic function index (SFI), grip strength, and withdrawal reflex post-sciatic nerve crush injury. Furthermore, EPO-PLGA-PEG significantly increased blood vessel density, number of junctions, and myelinated nerve fibers after injury. CONCLUSION: This study provides promising preclinical evidence for using EPO-PLGA-PEG as a local controlled-release treatment to enhance functional outcomes and neurovascular regeneration in TPNI. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12951-022-01666-5.
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spelling pubmed-96174432022-10-30 Erythropoietin-PLGA-PEG as a local treatment to promote functional recovery and neurovascular regeneration after peripheral nerve injury Manto, Kristen M. Govindappa, Prem Kumar Martinazzi, Brandon Han, Aijie Hegarty, John P. Koroneos, Zachary Talukder, M. A. Hassan Elfar, John C. J Nanobiotechnology Research BACKGROUND: Traumatic peripheral nerve injury (TPNI) is a major medical problem with no universally accepted pharmacologic treatment. We hypothesized that encapsulation of pro-angiogenic erythropoietin (EPO) in amphiphilic PLGA-PEG block copolymers could serve as a local controlled-release drug delivery system to enhance neurovascular regeneration after nerve injury. METHODS: In this study, we synthesized an EPO-PLGA-PEG block copolymer formulation. We characterized its physiochemical and release properties and examined its effects on functional recovery, neural regeneration, and blood vessel formation after sciatic nerve crush injury in mice. RESULTS: EPO-PLGA-PEG underwent solution-to-gel transition within the physiologically relevant temperature window and released stable EPO for up to 18 days. EPO-PLGA-PEG significantly enhanced sciatic function index (SFI), grip strength, and withdrawal reflex post-sciatic nerve crush injury. Furthermore, EPO-PLGA-PEG significantly increased blood vessel density, number of junctions, and myelinated nerve fibers after injury. CONCLUSION: This study provides promising preclinical evidence for using EPO-PLGA-PEG as a local controlled-release treatment to enhance functional outcomes and neurovascular regeneration in TPNI. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12951-022-01666-5. BioMed Central 2022-10-28 /pmc/articles/PMC9617443/ /pubmed/36307805 http://dx.doi.org/10.1186/s12951-022-01666-5 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Manto, Kristen M.
Govindappa, Prem Kumar
Martinazzi, Brandon
Han, Aijie
Hegarty, John P.
Koroneos, Zachary
Talukder, M. A. Hassan
Elfar, John C.
Erythropoietin-PLGA-PEG as a local treatment to promote functional recovery and neurovascular regeneration after peripheral nerve injury
title Erythropoietin-PLGA-PEG as a local treatment to promote functional recovery and neurovascular regeneration after peripheral nerve injury
title_full Erythropoietin-PLGA-PEG as a local treatment to promote functional recovery and neurovascular regeneration after peripheral nerve injury
title_fullStr Erythropoietin-PLGA-PEG as a local treatment to promote functional recovery and neurovascular regeneration after peripheral nerve injury
title_full_unstemmed Erythropoietin-PLGA-PEG as a local treatment to promote functional recovery and neurovascular regeneration after peripheral nerve injury
title_short Erythropoietin-PLGA-PEG as a local treatment to promote functional recovery and neurovascular regeneration after peripheral nerve injury
title_sort erythropoietin-plga-peg as a local treatment to promote functional recovery and neurovascular regeneration after peripheral nerve injury
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9617443/
https://www.ncbi.nlm.nih.gov/pubmed/36307805
http://dx.doi.org/10.1186/s12951-022-01666-5
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