Focal release of neurotrophic factors by biodegradable microspheres enhance motor and sensory axonal regeneration in vitro and in vivo

Neurotrophic factors (NTFs) promote nerve regeneration and neuronal survival after peripheral nerve injury. However, drawbacks related with administration and bioactivity during long periods limit their therapeutic application. In this study, PLGA microspheres (MPs) were used to locally release diff...

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Authors: Santos, Daniel, Giudetti, Guido|||0000-0002-4543-5871, Micera, Silvestro|||0000-0003-4396-8217, Navarro, X. (Xavier)|||0000-0001-9849-902X, Del Valle, Jaume|||0000-0002-6703-8244
Format: article
Publication Date:2016
Country:España
Institution:Universitat Autònoma de Barcelona
Repository:Dipòsit Digital de Documents de la UAB
Language:English
OAI Identifier:oai:ddd.uab.cat:147689
Online Access:https://ddd.uab.cat/record/147689
https://dx.doi.org/urn:doi:10.1016/j.brainres.2016.01.051
Access Level:Open access
Keyword:Growth factors
Microspheres
Motor axons
Nerve conduit
Nerve regeneration
Sensory axons
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spelling Focal release of neurotrophic factors by biodegradable microspheres enhance motor and sensory axonal regeneration in vitro and in vivoSantos, DanielGiudetti, Guido|||0000-0002-4543-5871Micera, Silvestro|||0000-0003-4396-8217Navarro, X. (Xavier)|||0000-0001-9849-902XDel Valle, Jaume|||0000-0002-6703-8244Growth factorsMicrospheresMotor axonsNerve conduitNerve regenerationSensory axonsNeurotrophic factors (NTFs) promote nerve regeneration and neuronal survival after peripheral nerve injury. However, drawbacks related with administration and bioactivity during long periods limit their therapeutic application. In this study, PLGA microspheres (MPs) were used to locally release different NTFs and evaluate whether they accelerate axonal regeneration in comparison with free NTFs or controls. ELISA, SEM, UV/visible light microscopy, organotypic cultures of DRG explants and spinal cord slices were used to characterize MP properties and the bioactivity of the released NTFs. Results of organotypic cultures showed that encapsulated NTFs maintain longer bioactivity and enhance neurite regeneration of both sensory and motor neurons compared with free NTFs. For in vivo assays, the rat sciatic nerve was transected and repaired with a silicone tube filled with collagen gel or collagen mixed with PBS encapsulated MPs (control groups) and with free or encapsulated NGF, BDNF, GDNF or FGF-2. After 20 days, a retrotracer was applied to the regenerated nerve to quantify motor and sensory axonal regeneration. NTF encapsulation in MPs improved regeneration of both motor and sensory axons, as evidenced by increased numbers of retrolabeled neurons. Hence, our results show that slow release of NTFs with PLGA MP enhance nerve regeneration. 22016-01-0120162016-01-01Articlehttp://purl.org/coar/resource_type/c_6501AMhttp://purl.org/coar/version/c_ab4af688f83e57aainfo:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/147689https://dx.doi.org/urn:doi:10.1016/j.brainres.2016.01.051reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengEuropean Commission https://doi.org/10.13039/501100000780 280778European Commission https://doi.org/10.13039/501100000780 611687open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.https://creativecommons.org/licenses/by-nc-nd/3.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:1476892026-06-06T12:50:31Z
dc.title.none.fl_str_mv Focal release of neurotrophic factors by biodegradable microspheres enhance motor and sensory axonal regeneration in vitro and in vivo
title Focal release of neurotrophic factors by biodegradable microspheres enhance motor and sensory axonal regeneration in vitro and in vivo
spellingShingle Focal release of neurotrophic factors by biodegradable microspheres enhance motor and sensory axonal regeneration in vitro and in vivo
Santos, Daniel
Growth factors
Microspheres
Motor axons
Nerve conduit
Nerve regeneration
Sensory axons
title_short Focal release of neurotrophic factors by biodegradable microspheres enhance motor and sensory axonal regeneration in vitro and in vivo
title_full Focal release of neurotrophic factors by biodegradable microspheres enhance motor and sensory axonal regeneration in vitro and in vivo
title_fullStr Focal release of neurotrophic factors by biodegradable microspheres enhance motor and sensory axonal regeneration in vitro and in vivo
title_full_unstemmed Focal release of neurotrophic factors by biodegradable microspheres enhance motor and sensory axonal regeneration in vitro and in vivo
title_sort Focal release of neurotrophic factors by biodegradable microspheres enhance motor and sensory axonal regeneration in vitro and in vivo
dc.creator.none.fl_str_mv Santos, Daniel
Giudetti, Guido|||0000-0002-4543-5871
Micera, Silvestro|||0000-0003-4396-8217
Navarro, X. (Xavier)|||0000-0001-9849-902X
Del Valle, Jaume|||0000-0002-6703-8244
author Santos, Daniel
author_facet Santos, Daniel
Giudetti, Guido|||0000-0002-4543-5871
Micera, Silvestro|||0000-0003-4396-8217
Navarro, X. (Xavier)|||0000-0001-9849-902X
Del Valle, Jaume|||0000-0002-6703-8244
author_role author
author2 Giudetti, Guido|||0000-0002-4543-5871
Micera, Silvestro|||0000-0003-4396-8217
Navarro, X. (Xavier)|||0000-0001-9849-902X
Del Valle, Jaume|||0000-0002-6703-8244
author2_role author
author
author
author
dc.subject.none.fl_str_mv Growth factors
Microspheres
Motor axons
Nerve conduit
Nerve regeneration
Sensory axons
topic Growth factors
Microspheres
Motor axons
Nerve conduit
Nerve regeneration
Sensory axons
description Neurotrophic factors (NTFs) promote nerve regeneration and neuronal survival after peripheral nerve injury. However, drawbacks related with administration and bioactivity during long periods limit their therapeutic application. In this study, PLGA microspheres (MPs) were used to locally release different NTFs and evaluate whether they accelerate axonal regeneration in comparison with free NTFs or controls. ELISA, SEM, UV/visible light microscopy, organotypic cultures of DRG explants and spinal cord slices were used to characterize MP properties and the bioactivity of the released NTFs. Results of organotypic cultures showed that encapsulated NTFs maintain longer bioactivity and enhance neurite regeneration of both sensory and motor neurons compared with free NTFs. For in vivo assays, the rat sciatic nerve was transected and repaired with a silicone tube filled with collagen gel or collagen mixed with PBS encapsulated MPs (control groups) and with free or encapsulated NGF, BDNF, GDNF or FGF-2. After 20 days, a retrotracer was applied to the regenerated nerve to quantify motor and sensory axonal regeneration. NTF encapsulation in MPs improved regeneration of both motor and sensory axons, as evidenced by increased numbers of retrolabeled neurons. Hence, our results show that slow release of NTFs with PLGA MP enhance nerve regeneration.
publishDate 2016
dc.date.none.fl_str_mv 2
2016-01-01
2016
2016-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
AM
http://purl.org/coar/version/c_ab4af688f83e57aa
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/147689
https://dx.doi.org/urn:doi:10.1016/j.brainres.2016.01.051
url https://ddd.uab.cat/record/147689
https://dx.doi.org/urn:doi:10.1016/j.brainres.2016.01.051
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv European Commission https://doi.org/10.13039/501100000780 280778
European Commission https://doi.org/10.13039/501100000780 611687
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc-nd/3.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc-nd/3.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
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repository.mail.fl_str_mv
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