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TY  - THES
AU  - Rama, Elena
TI  - Longitudinal monitoring of biohybrid tissue-engineered vascular grafts by multimodal molecular imaging
PB  - Rheinisch-Westfälische Technische Hochschule Aachen
VL  - Dissertation
CY  - Aachen
M1  - RWTH-2025-00260
SP  - 1 Online-Ressource : Illustrationen
PY  - 2024
N1  - Veröffentlicht auf dem Publikationsserver der RWTH Aachen University 2025
N1  - Dissertation, Rheinisch-Westfälische Technische Hochschule Aachen, 2024, Kumulative Dissertation
AB  - 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.
LB  - PUB:(DE-HGF)11
DO  - DOI:10.18154/RWTH-2025-00260
UR  - https://publications.rwth-aachen.de/record/1000244
ER  -