Engineering silk fibroin-based nerve conduit with neurotrophic factors for proximal protection after peripheral nerve injury

Detalhes bibliográficos
Autor(a) principal: Carvalho, Cristiana R.
Data de Publicação: 2020
Outros Autores: Chang, Wei, Silva-Correia, Joana, Oliveira, J. M., Reis, R. L., Kohn, Joachim
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/1822/68152
Resumo: Artificial nerve conduits capable of adequately releasing neurotrophic factors are extensively studied to bridge nerve defects. However, the lack of neurotrophic factors in the proximal area and their visible effects in axonal retrograde transport following nerve injury is one of the factors causing an incomplete nerve regeneration. Herein, an advanced conduit made of silk fibroin is produced, which can incorporate growth factors and promote an effective regeneration after injury. For that, enzymatically crosslinked silk fibroin-based conduits are developed to be used as a platform for the controlled delivery of neurotrophic factors. Nerve growth factor and glial-cell line derived neurotrophic factor (GDNF) are incorporated using two different methodologies: i) crosslinking and ii) absorption method. The release profile is measured by ELISA technique. The bioactivity of the neurotrophic factors is evaluated in vitro by using primary dorsal root ganglia. When implanted in a 10 mm sciatic nerve defect in rats, GDNF-loaded silk fibroin conduits reveal retrograde neuroprotection as compared to autografts and plain silk fibroin conduit. Therefore, the novel design presents a substantial improvement of retrograde trafficking, neuronsâ protection, and motor nerve reinnervation.
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spelling Engineering silk fibroin-based nerve conduit with neurotrophic factors for proximal protection after peripheral nerve injuryNerve guidance conduitsNeurotrophic factorsPeripheral nerve regenerationRetrograde transportSilk fibroinScience & TechnologyArtificial nerve conduits capable of adequately releasing neurotrophic factors are extensively studied to bridge nerve defects. However, the lack of neurotrophic factors in the proximal area and their visible effects in axonal retrograde transport following nerve injury is one of the factors causing an incomplete nerve regeneration. Herein, an advanced conduit made of silk fibroin is produced, which can incorporate growth factors and promote an effective regeneration after injury. For that, enzymatically crosslinked silk fibroin-based conduits are developed to be used as a platform for the controlled delivery of neurotrophic factors. Nerve growth factor and glial-cell line derived neurotrophic factor (GDNF) are incorporated using two different methodologies: i) crosslinking and ii) absorption method. The release profile is measured by ELISA technique. The bioactivity of the neurotrophic factors is evaluated in vitro by using primary dorsal root ganglia. When implanted in a 10 mm sciatic nerve defect in rats, GDNF-loaded silk fibroin conduits reveal retrograde neuroprotection as compared to autografts and plain silk fibroin conduit. Therefore, the novel design presents a substantial improvement of retrograde trafficking, neuronsâ protection, and motor nerve reinnervation.This work was supported by C.R.C.’s Ph.D. scholarship (Norte-08-5369-FSE-000037) and awarded FLAD scholarship (Proj. 29/2018). The FCTdistinctions attributed to J.M.O. (IF/00423/2012 and IF/01285/2015) andJ.S.-C. (IF/00115/2015) under the Investigador FCT program are alsogreatly acknowledged. The authors also thank Ijaz Ahmed from the BMEdepartment and Joe Steel from NJCBM, both from Rutgers University, fortheir important contribution in this scientific paper. The New Jersey Centerfor Biomaterials at Rutgers University provided additional support for this study. The authors acknowledge the project: “Nano-accelerated nerve re-generation and optogenetic empowering of neuromuscular functionality”(ref. PTDC/NAN-MAT/29936/2017).WileyUniversidade do MinhoCarvalho, Cristiana R.Chang, WeiSilva-Correia, JoanaOliveira, J. M.Reis, R. L.Kohn, Joachim2020-112020-11-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/68152engCarvalho C. R., Chang W., Silva-Correia J., Oliveira J. M., Reis R. L., Kohn J. Engineering Silk Fibroin-Based Nerve Conduit withNeurotrophic Factors for Proximal Protection afterPeripheral Nerve Injury, Advanced Healthcare Materials, Vol. 9, Issue 22, doi:10.1002/adhm.202000753, 20202192-26402192-265910.1002/adhm.20200075333169544https://onlinelibrary.wiley.com/doi/full/10.1002/adhm.202000753info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:00:14Zoai:repositorium.sdum.uminho.pt:1822/68152Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:50:05.680926Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Engineering silk fibroin-based nerve conduit with neurotrophic factors for proximal protection after peripheral nerve injury
title Engineering silk fibroin-based nerve conduit with neurotrophic factors for proximal protection after peripheral nerve injury
spellingShingle Engineering silk fibroin-based nerve conduit with neurotrophic factors for proximal protection after peripheral nerve injury
Carvalho, Cristiana R.
Nerve guidance conduits
Neurotrophic factors
Peripheral nerve regeneration
Retrograde transport
Silk fibroin
Science & Technology
title_short Engineering silk fibroin-based nerve conduit with neurotrophic factors for proximal protection after peripheral nerve injury
title_full Engineering silk fibroin-based nerve conduit with neurotrophic factors for proximal protection after peripheral nerve injury
title_fullStr Engineering silk fibroin-based nerve conduit with neurotrophic factors for proximal protection after peripheral nerve injury
title_full_unstemmed Engineering silk fibroin-based nerve conduit with neurotrophic factors for proximal protection after peripheral nerve injury
title_sort Engineering silk fibroin-based nerve conduit with neurotrophic factors for proximal protection after peripheral nerve injury
author Carvalho, Cristiana R.
author_facet Carvalho, Cristiana R.
Chang, Wei
Silva-Correia, Joana
Oliveira, J. M.
Reis, R. L.
Kohn, Joachim
author_role author
author2 Chang, Wei
Silva-Correia, Joana
Oliveira, J. M.
Reis, R. L.
Kohn, Joachim
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade do Minho
dc.contributor.author.fl_str_mv Carvalho, Cristiana R.
Chang, Wei
Silva-Correia, Joana
Oliveira, J. M.
Reis, R. L.
Kohn, Joachim
dc.subject.por.fl_str_mv Nerve guidance conduits
Neurotrophic factors
Peripheral nerve regeneration
Retrograde transport
Silk fibroin
Science & Technology
topic Nerve guidance conduits
Neurotrophic factors
Peripheral nerve regeneration
Retrograde transport
Silk fibroin
Science & Technology
description Artificial nerve conduits capable of adequately releasing neurotrophic factors are extensively studied to bridge nerve defects. However, the lack of neurotrophic factors in the proximal area and their visible effects in axonal retrograde transport following nerve injury is one of the factors causing an incomplete nerve regeneration. Herein, an advanced conduit made of silk fibroin is produced, which can incorporate growth factors and promote an effective regeneration after injury. For that, enzymatically crosslinked silk fibroin-based conduits are developed to be used as a platform for the controlled delivery of neurotrophic factors. Nerve growth factor and glial-cell line derived neurotrophic factor (GDNF) are incorporated using two different methodologies: i) crosslinking and ii) absorption method. The release profile is measured by ELISA technique. The bioactivity of the neurotrophic factors is evaluated in vitro by using primary dorsal root ganglia. When implanted in a 10 mm sciatic nerve defect in rats, GDNF-loaded silk fibroin conduits reveal retrograde neuroprotection as compared to autografts and plain silk fibroin conduit. Therefore, the novel design presents a substantial improvement of retrograde trafficking, neuronsâ protection, and motor nerve reinnervation.
publishDate 2020
dc.date.none.fl_str_mv 2020-11
2020-11-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/1822/68152
url http://hdl.handle.net/1822/68152
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Carvalho C. R., Chang W., Silva-Correia J., Oliveira J. M., Reis R. L., Kohn J. Engineering Silk Fibroin-Based Nerve Conduit withNeurotrophic Factors for Proximal Protection afterPeripheral Nerve Injury, Advanced Healthcare Materials, Vol. 9, Issue 22, doi:10.1002/adhm.202000753, 2020
2192-2640
2192-2659
10.1002/adhm.202000753
33169544
https://onlinelibrary.wiley.com/doi/full/10.1002/adhm.202000753
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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