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Angiogenic responses are enhanced in mechanically and microscopically characterized, microbial transglutaminase crosslinked collagen matrices with increased stiffness

Paper ID Volume ID Publish Year Pages File Format Full-Text
514 46 2013 13 PDF Available
Title
Angiogenic responses are enhanced in mechanically and microscopically characterized, microbial transglutaminase crosslinked collagen matrices with increased stiffness
Abstract

During angiogenesis, endothelial cells (ECs) use both soluble and insoluble cues to expand the existing vascular network to meet the changing trophic needs of the tissue. Fundamental to this expansion are physical interactions between ECs and extracellular matrix (ECM) that influence sprout migration, lumen formation and stabilization. These physical interactions suggest that ECM mechanical properties may influence sprouting ECs and, therefore, angiogenic responses. In a three-dimensional angiogenic model in which a monolayer of ECs is induced to invade an underlying collagen matrix, angiogenic responses were measured as a function of collagen matrix stiffness by inducing collagen crosslinking with microbial transglutaminase (mTG). By biaxial mechanical testing, stiffer collagen matrices were measured with both mTG treatment and incubation time. Using two-photon excited fluorescence (TPF) and second harmonic generation (SHG), it was shown that collagen TPF intensity increased with mTG treatment, and the TPF/SHG ratio correlated with biaxially tested mechanical stiffness. SHG and OCM were further used to show that other ECM physical properties such as porosity and pore size did not change with mTG treatment, thus verifying that matrix stiffness was tuned independently of matrix density. The results showed that stiffer matrices promote more angiogenic sprouts that invade deeper. No differences in lumen size were observed between control and mTG stiffened matrices, but greater remodeling was revealed in stiffer gels using SHG and OCM. The results of this study show that angiogenic responses are influenced by stiffness and suggest that ECM properties may be useful in regenerative medicine applications to engineer angiogenesis.

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Keywords
Angiogenesis; Second harmonic generation; Two-photon excited fluorescence; Collagen; Microbial transglutaminase
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Angiogenic responses are enhanced in mechanically and microscopically characterized, microbial transglutaminase crosslinked collagen matrices with increased stiffness
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Publisher
Database: Elsevier - ScienceDirect
Journal: Acta Biomaterialia - Volume 9, Issue 7, July 2013, Pages 7178–7190
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