TY - JOUR
T1 - In vitro and in vivo evaluation of biohybrid tissue-engineered vascular grafts with transformative 1H/19F MRI traceable scaffolds
AU - Rama, Elena
AU - Mohapatra, Saurav Ranjan
AU - Sugimura, Yukiharu
AU - Suzuki, Tomoyuki
AU - Siebert, Stefan
AU - Barmin, Roman
AU - Hermann, Juliane
AU - Baier, Jasmin
AU - Rix, Anne
AU - Lemainque, Teresa
AU - Koletnik, Susanne
AU - Elshafei, Asmaa Said
AU - Pallares, Roger Molto
AU - Dadfar, Seyed Mohammadali
AU - Tolba, René H.
AU - Schulz, Volkmar
AU - Jankowski, Joachim
AU - Apel, Christian
AU - Akhyari, Payam
AU - Jockenhoevel, Stefan
AU - Kiessling, Fabian
N1 - Funding Information:
Subsequently, we investigated whether the resorption of SPION-PLGA fibers could be longitudinally monitored and the 19F signal of the permanent scaffold component (19F-TPU) remained stable. As previously described, 19F-TPU fibers were knitted onto the SPION-PLGA and PVDF textile scaffolds following three different designs to further investigate the effects of SPION-PLGA degradation on 19F signal detection (Fig. 3). 19F-TPU fiber signal intensities measured by 19F-UTE sequence did not significantly change, indicating that the 19F-TPU remained stable over the observation period (Fig. 3A; Table S1, Supporting Information). In contrast, PLGA fibers degraded throughout the observation time, which is clearly visible in R2 colormaps superimposed to 1H-T2-weighted images (Fig. 3B; Table S1, Supporting Information). VG_SPION and unlabeled VG were used as additional negative controls (Fig. 3B; Table S1, Supporting Information). As postulated, the MR signal of 19F-TPU remained constant throughout the observation period and was not influenced by the degrading SPION-PLGA fibers.This work was supported by the German Research Foundation in the Package Proposals PAK 961 (DFG \u2013 Project number: 403039938) to F.K and S.J, by the Transregional Collaborative Research Centre (TRR 219; Project-ID 322900939) to J.J. (subproject S-03 and C-04), and V.J. (subproject S-03, INST 948/4S-1 FU6.6). This research project is also supported by a grant from the Interdisciplinary Centre for Clinical Research within the faculty of Medicine at the RWTH Aachen University (OC1-11), by the START-Program of the Faculty of Medicine of the RWTH Aachen University, by a grant from the Interdisciplinary Centre for Clinical Research within the faculty of Medicine at the RWTH Aachen University (PTD 1-1), by ANR, BMBF, BMG, FWF, and Vinnova, under the frame ERA-PerMed (ERA-PERMED2022-202-KidneySign; Project-ID 2523FSB112).
Funding Information:
This work was supported by the German Research Foundation in the Package Proposals PAK 961 (DFG \u2013 Project number: 403039938) to F.K and S.J, by the Transregional Collaborative Research Centre (TRR 219; Project-ID 322900939) to J.J. (subproject S-03 and C-04), and V.J. (subproject S-03, INST 948/4S-1 FU6.6). This research project is also supported by a grant from the Interdisciplinary Centre for Clinical Research within the faculty of Medicine at the RWTH Aachen University (OC1-11), by the START-Program of the Faculty of Medicine of the RWTH Aachen University, by a grant from the Interdisciplinary Centre for Clinical Research within the faculty of Medicine at the RWTH Aachen University (PTD 1-1), by ANR, BMBF, BMG, FWF, and Vinnova, under the frame ERA-PerMed (ERA-PERMED2022-202-KidneySign; Project-ID 2523FSB112).
Publisher Copyright:
© 2024 The Authors
PY - 2024/12/1
Y1 - 2024/12/1
N2 - Biohybrid tissue-engineered vascular grafts (TEVGs) promise long-term durability due to their ability to adapt to hosts' needs. However, the latter calls for sensitive non-invasive imaging approaches to longitudinally monitor their functionality, integrity, and positioning. Here, we present an imaging approach comprising the labeling of non-degradable and degradable TEVGs' components for their in vitro and in vivo monitoring by hybrid 1H/19F MRI. TEVGs (inner diameter 1.5 mm) consisted of biodegradable poly(lactic-co-glycolic acid) (PLGA) fibers passively incorporating superparamagnetic iron oxide nanoparticles (SPIONs), non-degradable polyvinylidene fluoride scaffolds labeled with highly fluorinated thermoplastic polyurethane (19F-TPU) fibers, a smooth muscle cells containing fibrin blend, and endothelial cells. 1H/19F MRI of TEVGs in bioreactors, and after subcutaneous and infrarenal implantation in rats, revealed that PLGA degradation could be faithfully monitored by the decreasing SPIONs signal. The 19F signal of 19F-TPU remained constant over weeks. PLGA degradation was compensated by cells’ collagen and a-smooth-muscle-actin deposition. Interestingly, only TEVGs implanted on the abdominal aorta contained elastin. XTT and histology proved that our imaging markers did not influence extracellular matrix deposition and host immune reaction. This concept of non-invasive longitudinal assessment of cardiovascular implants using 1H/19F MRI might be applicable to various biohybrid tissue-engineered implants, facilitating their clinical translation.
AB - Biohybrid tissue-engineered vascular grafts (TEVGs) promise long-term durability due to their ability to adapt to hosts' needs. However, the latter calls for sensitive non-invasive imaging approaches to longitudinally monitor their functionality, integrity, and positioning. Here, we present an imaging approach comprising the labeling of non-degradable and degradable TEVGs' components for their in vitro and in vivo monitoring by hybrid 1H/19F MRI. TEVGs (inner diameter 1.5 mm) consisted of biodegradable poly(lactic-co-glycolic acid) (PLGA) fibers passively incorporating superparamagnetic iron oxide nanoparticles (SPIONs), non-degradable polyvinylidene fluoride scaffolds labeled with highly fluorinated thermoplastic polyurethane (19F-TPU) fibers, a smooth muscle cells containing fibrin blend, and endothelial cells. 1H/19F MRI of TEVGs in bioreactors, and after subcutaneous and infrarenal implantation in rats, revealed that PLGA degradation could be faithfully monitored by the decreasing SPIONs signal. The 19F signal of 19F-TPU remained constant over weeks. PLGA degradation was compensated by cells’ collagen and a-smooth-muscle-actin deposition. Interestingly, only TEVGs implanted on the abdominal aorta contained elastin. XTT and histology proved that our imaging markers did not influence extracellular matrix deposition and host immune reaction. This concept of non-invasive longitudinal assessment of cardiovascular implants using 1H/19F MRI might be applicable to various biohybrid tissue-engineered implants, facilitating their clinical translation.
KW - 19 F-TPU
KW - Hybrid H/ F MRI 1 19
KW - Molecular imaging
KW - PLGA
KW - SPIONs
KW - Tissue-engineering
U2 - 10.1016/j.biomaterials.2024.122669
DO - 10.1016/j.biomaterials.2024.122669
M3 - Article
SN - 0142-9612
VL - 311
JO - Biomaterials
JF - Biomaterials
M1 - 122669
ER -