Bioactive 3D Scaffolds for the Delivery of NGF and BDNF to Improve Nerve Regeneration

Peripheral nerve injury is an important cause of disability, that can hinder significantly sensory and motor function. The clinical gold standard for peripheral nerve repair is the use of autografts, nevertheless, this method has limitations such as donor site morbidity. An emerging alternative to a...

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Main Authors: Ana M. Sandoval-Castellanos, Frederik Claeyssens, John W. Haycock
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-10-01
Series:Frontiers in Materials
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fmats.2021.734683/full
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author Ana M. Sandoval-Castellanos
Frederik Claeyssens
John W. Haycock
author_facet Ana M. Sandoval-Castellanos
Frederik Claeyssens
John W. Haycock
author_sort Ana M. Sandoval-Castellanos
collection DOAJ
description Peripheral nerve injury is an important cause of disability, that can hinder significantly sensory and motor function. The clinical gold standard for peripheral nerve repair is the use of autografts, nevertheless, this method has limitations such as donor site morbidity. An emerging alternative to autografts are nerve guide conduits, which are used to entubulate the severed nerve and provide guidance for the directed regeneration of the nerve tissue. These nerve guide conduits are less effective than autografts, and to enhance their performance the incorporation of neurotrophins can be considered. To enable optimal nerve regeneration, it is important to continuously stimulate neurite outgrowth by designing a delivery system for the sustained delivery of neurotrophins. The aim of this study was to develop a novel bioactive surface on electrospun fibres to supply a sustained release of heparin bound NGF or BDNF electrostatically immobilised onto an amine functionalized surface to encourage neurite outgrowth and Schwann cell migration. The bioactive surface was characterised by XPS analysis and ELISA. To assess the effect of the bioactive surface on electrospun fibres, primary chick embryo dorsal root ganglia were used, and neurite outgrowth and Schwann cell migration were measured. Our results showed a significant improvement regarding nerve regeneration, with the growth of neurites of up to 3 mm in 7 days, accompanied by Schwann cells. We hypothesize that the physical guidance provided by the fibres along the sustained delivery of NGF or BDNF created a stimulatory environment for nerve regeneration. Our results were achieved by immobilising relatively low concentrations of neurotrophins (1 ng/ml), which provides a promising, low-cost, and scalable method to improve current nerve guide conduits.
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spelling doaj.art-3d211ff82a6945d4a9fb43701eb7e0162022-12-21T21:35:13ZengFrontiers Media S.A.Frontiers in Materials2296-80162021-10-01810.3389/fmats.2021.734683734683Bioactive 3D Scaffolds for the Delivery of NGF and BDNF to Improve Nerve RegenerationAna M. Sandoval-CastellanosFrederik ClaeyssensJohn W. HaycockPeripheral nerve injury is an important cause of disability, that can hinder significantly sensory and motor function. The clinical gold standard for peripheral nerve repair is the use of autografts, nevertheless, this method has limitations such as donor site morbidity. An emerging alternative to autografts are nerve guide conduits, which are used to entubulate the severed nerve and provide guidance for the directed regeneration of the nerve tissue. These nerve guide conduits are less effective than autografts, and to enhance their performance the incorporation of neurotrophins can be considered. To enable optimal nerve regeneration, it is important to continuously stimulate neurite outgrowth by designing a delivery system for the sustained delivery of neurotrophins. The aim of this study was to develop a novel bioactive surface on electrospun fibres to supply a sustained release of heparin bound NGF or BDNF electrostatically immobilised onto an amine functionalized surface to encourage neurite outgrowth and Schwann cell migration. The bioactive surface was characterised by XPS analysis and ELISA. To assess the effect of the bioactive surface on electrospun fibres, primary chick embryo dorsal root ganglia were used, and neurite outgrowth and Schwann cell migration were measured. Our results showed a significant improvement regarding nerve regeneration, with the growth of neurites of up to 3 mm in 7 days, accompanied by Schwann cells. We hypothesize that the physical guidance provided by the fibres along the sustained delivery of NGF or BDNF created a stimulatory environment for nerve regeneration. Our results were achieved by immobilising relatively low concentrations of neurotrophins (1 ng/ml), which provides a promising, low-cost, and scalable method to improve current nerve guide conduits.https://www.frontiersin.org/articles/10.3389/fmats.2021.734683/fullbioactive surfaceNGF (nerve growth factor)BDNF (brain derived neurotrophic factor)nerve regenerationdrug deliverysurface coating
spellingShingle Ana M. Sandoval-Castellanos
Frederik Claeyssens
John W. Haycock
Bioactive 3D Scaffolds for the Delivery of NGF and BDNF to Improve Nerve Regeneration
Frontiers in Materials
bioactive surface
NGF (nerve growth factor)
BDNF (brain derived neurotrophic factor)
nerve regeneration
drug delivery
surface coating
title Bioactive 3D Scaffolds for the Delivery of NGF and BDNF to Improve Nerve Regeneration
title_full Bioactive 3D Scaffolds for the Delivery of NGF and BDNF to Improve Nerve Regeneration
title_fullStr Bioactive 3D Scaffolds for the Delivery of NGF and BDNF to Improve Nerve Regeneration
title_full_unstemmed Bioactive 3D Scaffolds for the Delivery of NGF and BDNF to Improve Nerve Regeneration
title_short Bioactive 3D Scaffolds for the Delivery of NGF and BDNF to Improve Nerve Regeneration
title_sort bioactive 3d scaffolds for the delivery of ngf and bdnf to improve nerve regeneration
topic bioactive surface
NGF (nerve growth factor)
BDNF (brain derived neurotrophic factor)
nerve regeneration
drug delivery
surface coating
url https://www.frontiersin.org/articles/10.3389/fmats.2021.734683/full
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