Non-invasive and real-time measurement of microvascular barrier in intact lungs.
Bioreactor
Ex vivo
Lung
Mathematical model
Microvascular
Tissue engineering
Journal
Biomaterials
ISSN: 1878-5905
Titre abrégé: Biomaterials
Pays: Netherlands
ID NLM: 8100316
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
received:
04
02
2019
revised:
25
06
2019
accepted:
27
06
2019
pubmed:
8
7
2019
medline:
24
9
2020
entrez:
8
7
2019
Statut:
ppublish
Résumé
Microvascular leak is a phenomenon witnessed in multiple disease states. In organ engineering, regaining a functional barrier is the most crucial step towards creating an implantable organ. All previous methods of measuring microvascular permeability were either invasive, lengthy, introduced exogenous macromolecules, or relied on extrapolations from cultured cells. We present here a system that enables real-time measurement of microvascular permeability in intact rat lungs. Our unique system design allows direct, non-invasive measurement of average alveolar and capillary pressures, tracks flow paths within the organ, and enables calculation of lumped internal resistances including microvascular barrier. We first describe the physiology of native and decellularized lungs and the inherent properties of the extracellular matrix as functions of perfusion rate. We next track changing internal resistances and flows in injured native rat lungs, resolving the onset of microvascular leak, quantifying changing vascular resistances, and identifying distinct phases of organ failure. Finally, we measure changes in permeability within engineered lungs seeded with microvascular endothelial cells, quantifying cellular effects on internal vascular and barrier resistances over time. This system marks considerable progress in bioreactor design for intact organs and may be used to monitor and garner physiological insights into native, decellularized, and engineered tissues.
Identifiants
pubmed: 31280072
pii: S0142-9612(19)30412-0
doi: 10.1016/j.biomaterials.2019.119313
pmc: PMC6863174
mid: NIHMS1534468
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
119313Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL138540
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007205
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM086287
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.
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