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The influence of ascorbic acid, TGF-β1, and cell-mediated remodeling on the bulk mechanical properties of 3-D PEG–fibrinogen constructs

Paper ID Volume ID Publish Year Pages File Format Full-Text
8791 606 2009 11 PDF Available
Title
The influence of ascorbic acid, TGF-β1, and cell-mediated remodeling on the bulk mechanical properties of 3-D PEG–fibrinogen constructs
Abstract

Two-dimensional cell culture studies have shown that matrix rigidity can influence cell function, but little is known about how matrix physical properties, and their changes with time, influence cell function in 3-D. Biosynthetic hydrogels based on PEGylated fibrinogen permit the initial decoupling of matrix chemical and mechanical properties, and are thus potentially attractive for addressing this question. However, the mechanical stability of these gels due to passive hydrolysis and cell-mediated remodeling has not previously been addressed. Here, we show that the bulk mechanical properties of acellular PEG–fibrinogen hydrogels significantly decrease over time in PBS regardless of matrix cross-linking density in 7 days. To compensate, smooth muscle cells (SMCs) were encapsulated and stimulated to produce their own matrix using ascorbic acid or TGF-β1. Ascorbic acid treatment improved the mechanical properties of the constructs after 14 days in less cross-linked matrices, but TGF-β1 did not. The increase in matrix modulus of the constructs was not due to an increase in type I collagen deposition, which remained low and pericellular regardless of cross-link density or the soluble factor applied. Instead, ascorbic acid, but not TGF-β1, preferentially enhanced the contractile SMC phenotype in the less cross-linked gels. Inhibition of contractility reduced cell spreading and the expression of contractile markers, and eliminated any beneficial increase in matrix modulus induced by cell-generated contraction of the gels. Together, these data show that PEG–fibrinogen hydrogels are susceptible to both hydrolysis and proteolysis, and suggest that some soluble factors may stimulate matrix remodeling by modulating SMC phenotype instead of inducing ECM synthesis in a 3-D matrix.

Keywords
Polyethylene oxide; Fibrinogen; ECM (extracellular matrix); Smooth muscle cell; TGF (transforming growth factor)
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The influence of ascorbic acid, TGF-β1, and cell-mediated remodeling on the bulk mechanical properties of 3-D PEG–fibrinogen constructs
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 30, Issues 23–24, August 2009, Pages 3854–3864
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us