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Electrospun Decellularized Lung Matrix Scaffold for Airway Smooth Muscle Culture
journal contribution
posted on 2017-11-13, 00:00 authored by Bethany
M. Young, Keerthana Shankar, Brittany P. Allen, Robert A. Pouliot, Matthew B. Schneck, Nabil S. Mikhaiel, Rebecca L. HeiseChronic
respiratory disease affects many people worldwide with
little known about the intricate mechanisms driving the pathology,
making it difficult to develop novel therapies. Improving the understanding
of airway smooth muscle and extracellular matrix (ECM) interactions
is key to developing treatments for this leading cause of death. With
currently no relevant or controllable in vivo or in vitro models to investigate cell–ECM interactions
in the small airways, the development of a biomimetic in vitro model with cell attachment, signaling, and organization is needed.
The goal of this study was to create a biologically and structurally
relevant in vitro model of small airway smooth muscle.
In order to achieve this goal, a scaffold was engineered from synthetic
poly-l-lactic acid (PLLA) and decellularized pig lung ECM
(PLECM). PLECM scaffolds have improved physical characteristics over
synthetic scaffolds, by exhibiting a significant decrease in the elastic
modulus and an increase in hydrophilicity. Histological staining and
SDS-PAGE showed that essential proteins or protein fragments found
in natural ECM were present after processing. Human bronchial smooth
muscle cells (HBSMCs) seeded onto PLECM 3D scaffolds formed confluent
layers and maintained a contractile phenotype, as demonstrated by
the organized arrangement of actin filaments within the cell and expected
contractile protein expression of calponin 1. HBSMCs cultured on electrospun
PLECM scaffold also increased alpha-1 type 1 collagen compared to
those cultured on PLLA scaffolds. In summary, this research demonstrates
that a PLLA/PLECM composite electrospun mat is a promising tool to
produce an in vitro model of the airway with the
potential for a better understanding of bronchiole smooth muscle behavior
in diseased or normal states.
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electrospun PLECM scaffoldtype 1 collagencalponin 1. HBSMCsactin filamentsPLECM 3 D scaffoldscontractile phenotypecontractile protein expressionairwayElectrospun Decellularized Lung Matrix ScaffoldHistological stainingmuscle cellsPLECM scaffoldsAirway Smooth Muscle Culture Chroniccell attachmentmuscle behaviorelectrospun matextracellular matrixpoly-l-lactic acidprotein fragmentsSDS-PAGEnovel therapiesdecellularized pig lung ECMmodelPLLA scaffolds
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