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Investigating the Potential of Off-the-Shelf Tissue Engineered
Cardiovascular Graft Materials
L.M. Davis, G.T. Carroll, A. Callanan, B.J. Doyle, M.T. Walsh, T.M. McGloughlin
Centre for Applied Biomedical Engineering Research (CABER), Department of Mechanical,
Aeronautical and Biomedical Engineering, Materials and Surface Science Institute (MSSI),
University of Limerick, Ireland
Laura.Davis@ul.ie
Abstract
Effective vascular tissue replacements for the treatment
of cardiovascular disease are still an unaddressed
worldwide problem. Naturally derived biological
scaffolds offer huge potential although a major problem
of using such scaffolds is storage, particularly in a
hydrated and stented configuration, which can result in
biomechanical changes in the scaffolds. This study
analysed the mechanical and bioactive effects of
hydrated storage of two scaffolds, small intestinal
submucosa (SIS) and urinary bladder matrix (UBM) in
both stented and un-stented configurations for up to
4-months.
1. Introduction
Established treatment modalities for cardiovascular
diseases include arterial substitutes and synthetic graft
materials but these have associated issues such as low
patency and compliance mismatch. Currently, there is a
shift towards a tissue engineering approach in the form
of acellular extracellular (ECM) based vascular grafts
with such materials offering many mechanical, chemical
and biological advantages over their synthetic
counterparts. In order for these to be successful, a
suitable biocompatible storage environment is required
to allow migration, adhesion and proliferation of host
cells upon material implantation.
2. Methodology
Multilayered ECM scaffolds (UBM and SIS) were
immersed in a hydrating solution in stented and
un-stented configurations simulating the catheter
environment for periods of up to 4-months. Mechanical
evaluation was conducted with dog-bone specimens
pre-conditioned to align the material fibres and loaded
until failure. Cell culture evaluation was carried out
using human aortic endothelial cells (HAEC). Cellular
metabolic activity and proliferation was examined using
alamarBlue ® cell viability reagent for up to 96-hours in
culture. Furthermore, the concentration of various
nucleic acids and proteins leached during storage were
analysed utilising a NanoDrop spectrophotometer.
3. Results
Upon deployment, uniform radial loading of the stent
on the ECM samples was verified. Favourably, the
average UTS of all ECM samples evaluated were noted
62
to be above the average aortic tissue failure strength.
Cellular performance analysis indicated that stored
ECM scaffolds exhibit a positive cellular bioactivity
when compared with the lyophilised controls.
Figure 1 Cellular metabolic activity after 72-hours in culture
due to hydrated storage of up to 4-months.
Significance was not observed in the mechanical and
cellular results between stented and un-stented
conditions, indicating that these ECM materials may
also offer potential as a scaffold material in minimally
invasive treatments approaches.
4. Discussion
Upon storage, naturally derived scaffolds are
susceptible to degradation resulting in altered
micro-structure and mechanical properties. This study
has demonstrated that ECM materials under storage and
stenting environments retain sufficient mechanical
integrity and cellular performance indicating that long
term storage of such materials has no negative effect
under the parameters investigated. Thus, based on the
findings from this study, ECM materials such as SIS and
UBM have potential as treatment modalities for
cardiovascular disease. Furthermore, such tissue
engineered scaffolds offer great potential as an off-theshelf
implant and for use in minimally invasive
treatment approaches.
8. References
Badylak et al. J Surg Res 47(1):74-80, 1989.
Freytes et al. J Biomed Mater Res 78B(2):327-333, 2006.
Davis et al. 6 th World Congress on Biomechanics, pp.139-
142, Singapore, 2010.
This work was funded by Enterprise Ireland Technology Development Grant
CFTD 2007 131 and the European Regional Development Fund. ECM material
was generously donated by Prof. Badylak from the McGowan Institute for
Regenerative Medicine, University of Pittsburgh, USA.