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@PHDTHESIS{Rama:1000244,
author = {Rama, Elena},
othercontributors = {Kiessling, Fabian and Jockenhoevel, Stefan},
title = {{L}ongitudinal monitoring of biohybrid tissue-engineered
vascular grafts by multimodal molecular imaging},
school = {Rheinisch-Westfälische Technische Hochschule Aachen},
type = {Dissertation},
address = {Aachen},
publisher = {RWTH Aachen University},
reportid = {RWTH-2025-00260},
pages = {1 Online-Ressource : Illustrationen},
year = {2024},
note = {Veröffentlicht auf dem Publikationsserver der RWTH Aachen
University 2025; Dissertation, Rheinisch-Westfälische
Technische Hochschule Aachen, 2024, Kumulative Dissertation},
abstract = {Tissue-engineered vascular grafts (TEVGs) represent a
significant advancement in cardiovascular surgery by
offering long-term durability through their ability to grow,
adapt, and remodel in response to the host's needs. TEVGs
achieve this by combining synthetic polymers with biological
components, which provides a balanced compromise between
high structural stability and biological adaptability.
However, successful clinical implementation requires
sensitive, non-invasive imaging to monitor the
functionality, integrity, and positioning of these grafts
over time, from late in vitro maturation to early in vivo
engraftment. A novel comprehensive molecular imaging
approach has been developed to meet this need, employing
both magnetic resonance imaging (MRI) and ultrasound (US).
This strategy includes the incorporation of
superparamagnetic iron-oxide nanoparticles (SPIONs) within
biodegradable poly(lactic-co-glycolic acid) (PLGA) fibers,
which are electrospun onto a polyvinylidene fluoride (PVDF)
non-degradable scaffold. The textile scaffold is then molded
with a blend of smooth muscle cells (SMCs) and fibrin, and
its lumen is lined with endothelial cells (ECs). The SPIONs
enable quantitative monitoring of scaffold resorption via
MRI both in vitro and in vivo. Additionally, molecular MRI
using elastin- and collagen-targeted probes depicts
extracellular matrix (ECM) formation, providing insights
into the biological remodeling of the grafts. Molecular US
targeting αvβ3 integrins confirms endothelial integrity,
which is crucial to predict TEVG’s dysfunction that could
be induced by inflammatory factors such as TNF-α. Enhancing
this imaging strategy, a hybrid 1H/19F MRI approach has been
introduced to label and monitor both non-degradable and
biodegradable components of TEVGs. TEVGs, designed with an
inner diameter of 1.5 mm, consist of 1) biodegradable PLGA
fibers incorporating SPIONs, 2) non-degradable PVDF
scaffolds labeled with highly fluorinated thermoplastic
polyurethane (19F-TPU) fibers and 3) fibrin gel containing
SMCs and ECs. The dual MRI technique allows for quantitative
tracking of PLGA degradation, indicated by the decreasing
SPION signal, while the constant 19F signal ensures the
integrity of the non-degradable components over time both in
bioreactors and after subcutaneous and infrarenal
implantation in rats. The resorption of the PLGA was
effectively compensated by the deposition of collagen and
α-smooth-muscle-actin. Notably, elastin was detected only
in TEVGs implanted on the abdominal aorta, highlighting that
the interplay between mechanical stresses, constructive
signaling molecules (i.e., matrix-bound nanovesicles), and
inflammatory cells stimulate a more intense remodeling of
TEVGs, thus boosting an initial production of elastin.
Importantly, XTT assays and histological analyses confirmed
that the imaging markers did not adversely affect ECM
deposition or elicit an undesirable host immune response.In
conclusion, the successful application of non-invasive
molecular imaging to longitudinally evaluate TEVG
remodeling, combined with the innovative hybrid 1H/19F MRI
approach, provides a robust framework for ensuring proper
prosthesis engraftment. This imaging strategy offers a
comprehensive solution for monitoring TEVGs from in vitro
quality control to in vivo applications, significantly
enhancing the potential for clinical translation of
biohybrid tissue-engineered implants and similar
bioengineered constructs.},
cin = {811003-3 ; 924210},
ddc = {610},
cid = {$I:(DE-82)811003-3_20140620$},
pnm = {DFG project G:(GEPRIS)403039938 - TexValveMonitoring -
Multimodale longitudinale Bildgebung von biohybriden
Herzklappen (403039938)},
pid = {G:(GEPRIS)403039938},
typ = {PUB:(DE-HGF)11},
doi = {10.18154/RWTH-2025-00260},
url = {https://publications.rwth-aachen.de/record/1000244},
}
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