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Establishment of a pulmonary epithelial barrier on biodegradable poly-L-lactic-acid membranes

Establishment of a pulmonary epithelial barrier on biodegradable poly-L-lactic-acid membranes
Establishment of a pulmonary epithelial barrier on biodegradable poly-L-lactic-acid membranes
Development of biocompatible and functional scaffolds for tissue engineering is a major challenge, especially for development of polarised epithelia that are critical structures in tissue homeostasis. Different in vitro models of the lung epithelial barrier have been characterized using non-degradable polyethylene terephthalate membranes which limits their uses for tissue engineering. Although poly-L-lactic acid (PLLA) membranes are biodegradable, those prepared via conventional Diffusion Induced Phase Separation (DIPS) lack open-porous geometry and show limited permeability compromising their use for epithelial barrier studies. Here we used PLLA membranes prepared via a modification of the standard DIPS protocol to control the membrane surface morphology and permeability. These were bonded to cell culture inserts for use in barrier function studies. Pulmonary epithelial cells (H441) readily attached to the PLLA membranes and formed a confluent cell layer within two days. This was accompanied by a significant increase in trans-epithelial electrical resistance and correlated with the formation of tight junctions and vectorial cytokine secretion in response to TNFα. Our data suggest that a structurally polarized and functional epithelial barrier can be established on PLLA membranes produced via a non-standard DIPS protocol. Therefore, PLLA membranes have potential utility in lung tissue engineering applications requiring bio-absorbable membranes.
1932-6203
1-13
Conforti, Franco
28bf123c-e42a-4fb5-8b26-f79e1095c586
Davies, Donna
7de8fdc7-3640-4e3a-aa91-d0e03f990c38
Bucchieri, Fabio
3f85c9c8-2bc0-4fd0-b481-a03935fe3cb0
Montesanto, Salvo
dde1b3d1-4ffc-4602-9b43-71fe239ea063
Smithers, Natalie P
63ead01b-6515-4f82-a963-884f572af872
Brucato, Valerio
b45d1318-9c48-4fcb-9b08-00b4fb86fa04
la Carrubba, Vincenzo
d4eb36f4-8c46-4eca-a649-4a004b8e9212
Conforti, Franco
28bf123c-e42a-4fb5-8b26-f79e1095c586
Davies, Donna
7de8fdc7-3640-4e3a-aa91-d0e03f990c38
Bucchieri, Fabio
3f85c9c8-2bc0-4fd0-b481-a03935fe3cb0
Montesanto, Salvo
dde1b3d1-4ffc-4602-9b43-71fe239ea063
Smithers, Natalie P
63ead01b-6515-4f82-a963-884f572af872
Brucato, Valerio
b45d1318-9c48-4fcb-9b08-00b4fb86fa04
la Carrubba, Vincenzo
d4eb36f4-8c46-4eca-a649-4a004b8e9212

Conforti, Franco, Davies, Donna, Bucchieri, Fabio, Montesanto, Salvo, Smithers, Natalie P, Brucato, Valerio and la Carrubba, Vincenzo (2019) Establishment of a pulmonary epithelial barrier on biodegradable poly-L-lactic-acid membranes. PLoS ONE, 14 (1), 1-13, [e0210830]. (doi:10.1371/journal.pone.0210830).

Record type: Article

Abstract

Development of biocompatible and functional scaffolds for tissue engineering is a major challenge, especially for development of polarised epithelia that are critical structures in tissue homeostasis. Different in vitro models of the lung epithelial barrier have been characterized using non-degradable polyethylene terephthalate membranes which limits their uses for tissue engineering. Although poly-L-lactic acid (PLLA) membranes are biodegradable, those prepared via conventional Diffusion Induced Phase Separation (DIPS) lack open-porous geometry and show limited permeability compromising their use for epithelial barrier studies. Here we used PLLA membranes prepared via a modification of the standard DIPS protocol to control the membrane surface morphology and permeability. These were bonded to cell culture inserts for use in barrier function studies. Pulmonary epithelial cells (H441) readily attached to the PLLA membranes and formed a confluent cell layer within two days. This was accompanied by a significant increase in trans-epithelial electrical resistance and correlated with the formation of tight junctions and vectorial cytokine secretion in response to TNFα. Our data suggest that a structurally polarized and functional epithelial barrier can be established on PLLA membranes produced via a non-standard DIPS protocol. Therefore, PLLA membranes have potential utility in lung tissue engineering applications requiring bio-absorbable membranes.

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Accepted/In Press date: 9 January 2019
Published date: 17 January 2019

Identifiers

Local EPrints ID: 427470
URI: http://eprints.soton.ac.uk/id/eprint/427470
ISSN: 1932-6203
PURE UUID: f8bea1a4-2aab-45a3-84bc-d3efb902deee
ORCID for Donna Davies: ORCID iD orcid.org/0000-0002-5117-2991

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Date deposited: 17 Jan 2019 17:30
Last modified: 07 Oct 2020 01:32

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