Modelling-informed cell-seeded nerve repair construct designs for treating peripheral nerve injuries.

Millions of people worldwide are affected by peripheral nerve injuries (PNI), involving billions of dollars in healthcare costs. Common outcomes for patients include paralysis and loss of sensation, often leading to lifelong pain and disability. Engineered Neural Tissue (EngNT) is being developed as...

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Autores principales:	Rachel Coy, Maxime Berg, James B Phillips, Rebecca J Shipley
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/2a47eba674af43cba46556bdd0190069
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spelling	oai:doaj.org-article:2a47eba674af43cba46556bdd01900692021-12-02T19:57:34ZModelling-informed cell-seeded nerve repair construct designs for treating peripheral nerve injuries.1553-734X1553-735810.1371/journal.pcbi.1009142https://doaj.org/article/2a47eba674af43cba46556bdd01900692021-07-01T00:00:00Zhttps://doi.org/10.1371/journal.pcbi.1009142https://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Millions of people worldwide are affected by peripheral nerve injuries (PNI), involving billions of dollars in healthcare costs. Common outcomes for patients include paralysis and loss of sensation, often leading to lifelong pain and disability. Engineered Neural Tissue (EngNT) is being developed as an alternative to the current treatments for large-gap PNIs that show underwhelming functional recovery in many cases. EngNT repair constructs are composed of a stabilised hydrogel cylinder, surrounded by a sheath of material, to mimic the properties of nerve tissue. The technology also enables the spatial seeding of therapeutic cells in the hydrogel to promote nerve regeneration. The identification of mechanisms leading to maximal nerve regeneration and to functional recovery is a central challenge in the design of EngNT repair constructs. Using in vivo experiments in isolation is costly and time-consuming, offering a limited insight on the mechanisms underlying the performance of a given repair construct. To bridge this gap, we derive a cell-solute model and apply it to the case of EngNT repair constructs seeded with therapeutic cells which produce vascular endothelial growth factor (VEGF) under low oxygen conditions to promote vascularisation in the construct. The model comprises a set of coupled non-linear diffusion-reaction equations describing the evolving cell population along with its interactions with oxygen and VEGF fields during the first 24h after transplant into the nerve injury site. This model allows us to evaluate a wide range of repair construct designs (e.g. cell-seeding strategy, sheath material, culture conditions), the idea being that designs performing well over a short timescale could be shortlisted for in vivo trials. In particular, our results suggest that seeding cells beyond a certain density threshold is detrimental regardless of the situation considered, opening new avenues for future nerve tissue engineering.Rachel CoyMaxime BergJames B PhillipsRebecca J ShipleyPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 17, Iss 7, p e1009142 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Rachel Coy Maxime Berg James B Phillips Rebecca J Shipley Modelling-informed cell-seeded nerve repair construct designs for treating peripheral nerve injuries.
description	Millions of people worldwide are affected by peripheral nerve injuries (PNI), involving billions of dollars in healthcare costs. Common outcomes for patients include paralysis and loss of sensation, often leading to lifelong pain and disability. Engineered Neural Tissue (EngNT) is being developed as an alternative to the current treatments for large-gap PNIs that show underwhelming functional recovery in many cases. EngNT repair constructs are composed of a stabilised hydrogel cylinder, surrounded by a sheath of material, to mimic the properties of nerve tissue. The technology also enables the spatial seeding of therapeutic cells in the hydrogel to promote nerve regeneration. The identification of mechanisms leading to maximal nerve regeneration and to functional recovery is a central challenge in the design of EngNT repair constructs. Using in vivo experiments in isolation is costly and time-consuming, offering a limited insight on the mechanisms underlying the performance of a given repair construct. To bridge this gap, we derive a cell-solute model and apply it to the case of EngNT repair constructs seeded with therapeutic cells which produce vascular endothelial growth factor (VEGF) under low oxygen conditions to promote vascularisation in the construct. The model comprises a set of coupled non-linear diffusion-reaction equations describing the evolving cell population along with its interactions with oxygen and VEGF fields during the first 24h after transplant into the nerve injury site. This model allows us to evaluate a wide range of repair construct designs (e.g. cell-seeding strategy, sheath material, culture conditions), the idea being that designs performing well over a short timescale could be shortlisted for in vivo trials. In particular, our results suggest that seeding cells beyond a certain density threshold is detrimental regardless of the situation considered, opening new avenues for future nerve tissue engineering.
format	article
author	Rachel Coy Maxime Berg James B Phillips Rebecca J Shipley
author_facet	Rachel Coy Maxime Berg James B Phillips Rebecca J Shipley
author_sort	Rachel Coy
title	Modelling-informed cell-seeded nerve repair construct designs for treating peripheral nerve injuries.
title_short	Modelling-informed cell-seeded nerve repair construct designs for treating peripheral nerve injuries.
title_full	Modelling-informed cell-seeded nerve repair construct designs for treating peripheral nerve injuries.
title_fullStr	Modelling-informed cell-seeded nerve repair construct designs for treating peripheral nerve injuries.
title_full_unstemmed	Modelling-informed cell-seeded nerve repair construct designs for treating peripheral nerve injuries.
title_sort	modelling-informed cell-seeded nerve repair construct designs for treating peripheral nerve injuries.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/2a47eba674af43cba46556bdd0190069
work_keys_str_mv	AT rachelcoy modellinginformedcellseedednerverepairconstructdesignsfortreatingperipheralnerveinjuries AT maximeberg modellinginformedcellseedednerverepairconstructdesignsfortreatingperipheralnerveinjuries AT jamesbphillips modellinginformedcellseedednerverepairconstructdesignsfortreatingperipheralnerveinjuries AT rebeccajshipley modellinginformedcellseedednerverepairconstructdesignsfortreatingperipheralnerveinjuries
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Modelling-informed cell-seeded nerve repair construct designs for treating peripheral nerve injuries.

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