Gellan-Xanthan Hydrogel Conduits with Intraluminal Electrospun Nanofibers as Physical, Chemical and Therapeutic Cues for Peripheral Nerve Repair

Optimal levels of functional recovery in peripheral nerve injuries remain elusive due to the architectural complexity of the neuronal environment. Commercial nerve repair conduits lack essential guidance cues for the regenerating axons. In this study, the regenerative potential of a biosimulated ner...

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Autores principales:	Poornima Ramburrun, Pradeep Kumar, Elias Ndobe, Yahya E. Choonara
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	peripheral nerve regeneration biocompatibility functional recovery nerve repair conduits nanofibers intraluminal guidance Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/420e22084b3c4137bc87288196104903
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spelling	oai:doaj.org-article:420e22084b3c4137bc872881961049032021-11-11T17:02:14ZGellan-Xanthan Hydrogel Conduits with Intraluminal Electrospun Nanofibers as Physical, Chemical and Therapeutic Cues for Peripheral Nerve Repair10.3390/ijms2221115551422-00671661-6596https://doaj.org/article/420e22084b3c4137bc872881961049032021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11555https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Optimal levels of functional recovery in peripheral nerve injuries remain elusive due to the architectural complexity of the neuronal environment. Commercial nerve repair conduits lack essential guidance cues for the regenerating axons. In this study, the regenerative potential of a biosimulated nerve repair system providing three types of regenerative cues was evaluated in a 10 mm sciatic nerve-gap model over 4 weeks. A thermo-ionically crosslinked gellan-xanthan hydrogel conduit loaded with electrospun PHBV-magnesium oleate-N-acetyl-cysteine (PHBV-MgOl-NAC) nanofibers was assessed for mechanical properties, nerve growth factor (NGF) release kinetics and PC12 viability. In vivo functional recovery was based on walking track analysis, gastrocnemius muscle mass and histological analysis. As an intraluminal filler, PHBV-MgOl-NAC nanofibers improved matrix resilience, deformation and fracture of the hydrogel conduit. NGF release was sustained over 4 weeks, governed by Fickian diffusion and Case-II relaxational release for the hollow conduit and the nanofiber-loaded conduit, respectively. The intraluminal fibers supported PC12 proliferation by 49% compared to the control, preserved up to 43% muscle mass and gradually improved functional recovery. The combined elements of physical guidance (nanofibrous scaffolding), chemical cues (N-acetyl-cysteine and magnesium oleate) and therapeutic cues (NGF and diclofenac sodium) offers a promising strategy for the regeneration of severed peripheral nerves.Poornima RamburrunPradeep KumarElias NdobeYahya E. ChoonaraMDPI AGarticleperipheral nerve regenerationbiocompatibilityfunctional recoverynerve repair conduitsnanofibersintraluminal guidanceBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11555, p 11555 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	peripheral nerve regeneration biocompatibility functional recovery nerve repair conduits nanofibers intraluminal guidance Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	peripheral nerve regeneration biocompatibility functional recovery nerve repair conduits nanofibers intraluminal guidance Biology (General) QH301-705.5 Chemistry QD1-999 Poornima Ramburrun Pradeep Kumar Elias Ndobe Yahya E. Choonara Gellan-Xanthan Hydrogel Conduits with Intraluminal Electrospun Nanofibers as Physical, Chemical and Therapeutic Cues for Peripheral Nerve Repair
description	Optimal levels of functional recovery in peripheral nerve injuries remain elusive due to the architectural complexity of the neuronal environment. Commercial nerve repair conduits lack essential guidance cues for the regenerating axons. In this study, the regenerative potential of a biosimulated nerve repair system providing three types of regenerative cues was evaluated in a 10 mm sciatic nerve-gap model over 4 weeks. A thermo-ionically crosslinked gellan-xanthan hydrogel conduit loaded with electrospun PHBV-magnesium oleate-N-acetyl-cysteine (PHBV-MgOl-NAC) nanofibers was assessed for mechanical properties, nerve growth factor (NGF) release kinetics and PC12 viability. In vivo functional recovery was based on walking track analysis, gastrocnemius muscle mass and histological analysis. As an intraluminal filler, PHBV-MgOl-NAC nanofibers improved matrix resilience, deformation and fracture of the hydrogel conduit. NGF release was sustained over 4 weeks, governed by Fickian diffusion and Case-II relaxational release for the hollow conduit and the nanofiber-loaded conduit, respectively. The intraluminal fibers supported PC12 proliferation by 49% compared to the control, preserved up to 43% muscle mass and gradually improved functional recovery. The combined elements of physical guidance (nanofibrous scaffolding), chemical cues (N-acetyl-cysteine and magnesium oleate) and therapeutic cues (NGF and diclofenac sodium) offers a promising strategy for the regeneration of severed peripheral nerves.
format	article
author	Poornima Ramburrun Pradeep Kumar Elias Ndobe Yahya E. Choonara
author_facet	Poornima Ramburrun Pradeep Kumar Elias Ndobe Yahya E. Choonara
author_sort	Poornima Ramburrun
title	Gellan-Xanthan Hydrogel Conduits with Intraluminal Electrospun Nanofibers as Physical, Chemical and Therapeutic Cues for Peripheral Nerve Repair
title_short	Gellan-Xanthan Hydrogel Conduits with Intraluminal Electrospun Nanofibers as Physical, Chemical and Therapeutic Cues for Peripheral Nerve Repair
title_full	Gellan-Xanthan Hydrogel Conduits with Intraluminal Electrospun Nanofibers as Physical, Chemical and Therapeutic Cues for Peripheral Nerve Repair
title_fullStr	Gellan-Xanthan Hydrogel Conduits with Intraluminal Electrospun Nanofibers as Physical, Chemical and Therapeutic Cues for Peripheral Nerve Repair
title_full_unstemmed	Gellan-Xanthan Hydrogel Conduits with Intraluminal Electrospun Nanofibers as Physical, Chemical and Therapeutic Cues for Peripheral Nerve Repair
title_sort	gellan-xanthan hydrogel conduits with intraluminal electrospun nanofibers as physical, chemical and therapeutic cues for peripheral nerve repair
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/420e22084b3c4137bc87288196104903
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Gellan-Xanthan Hydrogel Conduits with Intraluminal Electrospun Nanofibers as Physical, Chemical and Therapeutic Cues for Peripheral Nerve Repair

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