Dataset Information

Monitoring the Remodeling of Biohybrid Tissue-Engineered Vascular Grafts by Multimodal Molecular Imaging.

ABSTRACT: Tissue-engineered vascular grafts (TEVGs) with the ability to grow and remodel open new perspectives for cardiovascular surgery. Equipping TEVGs with synthetic polymers and biological components provides a good compromise between high structural stability and biological adaptability. However, imaging approaches to control grafts' structural integrity, physiological function, and remodeling during the entire transition between late in vitro maturation and early in vivo engraftment are mandatory for clinical implementation. Thus, a comprehensive molecular imaging concept using magnetic resonance imaging (MRI) and ultrasound (US) to monitor textile scaffold resorption, extracellular matrix (ECM) remodeling, and endothelial integrity in TEVGs is presented here. Superparamagnetic iron-oxide nanoparticles (SPION) incorporated in biodegradable poly(lactic-co-glycolic acid) (PLGA) fibers of the TEVGs allow to quantitatively monitor scaffold resorption via MRI both in vitro and in vivo. Additionally, ECM formation can be depicted by molecular MRI using elastin- and collagen-targeted probes. Finally, molecular US of α_v β₃ integrins confirms the absence of endothelial dysfunction; the latter is provocable by TNF-α. In conclusion, the successful employment of noninvasive molecular imaging to longitudinally evaluate TEVGs remodeling is demonstrated. This approach may foster its translation from in vitro quality control assessment to in vivo applications to ensure proper prostheses engraftment.

SUBMITTER: Rama E

PROVIDER: S-EPMC8981893 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Publications

Monitoring the Remodeling of Biohybrid Tissue-Engineered Vascular Grafts by Multimodal Molecular Imaging.

Rama Elena E Mohapatra Saurav Ranjan SR Melcher Christoph C Nolte Teresa T Dadfar Seyed Mohammadali SM Brueck Ramona R Pathak Vertika V Rix Anne A Gries Thomas T Schulz Volkmar V Lammers Twan T Apel Christian C Jockenhoevel Stefan S Kiessling Fabian F

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20220204 10

Tissue-engineered vascular grafts (TEVGs) with the ability to grow and remodel open new perspectives for cardiovascular surgery. Equipping TEVGs with synthetic polymers and biological components provides a good compromise between high structural stability and biological adaptability. However, imaging approaches to control grafts' structural integrity, physiological function, and remodeling during the entire transition between late in vitro maturation and early in vivo engraftment are mandatory f ...[more]

PMID: 35119216

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Project description:Macrophages are a critical driver of neovessel formation in tissue-engineered vascular grafts (TEVGs), but also contribute to graft stenosis, a leading clinical trial complication. Macrophage depletion via liposomal delivery of clodronate, a first-generation bisphosphonate, mitigates stenosis, but simultaneously leads to a complete lack of tissue development in TEVGs. This result and the associated difficulty of utilizing liposomal delivery means that clodronate may not be an ideal means of preventing graft stenosis. Newer generation bisphosphonates, such as zoledronate, may have differential effects on graft development with more facile drug delivery. We sought to examine the effect of zoledronate on TEVG neotissue formation and its potential application for mitigating TEVG stenosis. Thus, mice implanted with TEVGs received zoledronate or no treatment and were monitored by serial ultrasound for graft dilation and stenosis. After two weeks, TEVGs were explanted for histological examination. The overall graft area and remaining graft material (polyglycolic-acid) were higher in the zoledronate treatment group. These effects were associated with a corresponding decrease in macrophage infiltration. In addition, zoledronate affected the deposition of collagen in TEVGs, specifically, total and mature collagen. These differences may be, in part, explained by a depletion of leukocytes within the bone marrow that subsequently led to a decrease in the number of tissue-infiltrating macrophages. TEVGs from zoledronate-treated mice demonstrated a significantly greater degree of smooth muscle cell presence. There was no statistical difference in graft patency between treatment and control groups. While zoledronate led to a decrease in the number of macrophages in the TEVGs, the severity of stenosis appears to have increased significantly. Zoledronate treatment demonstrates that the process of smooth muscle cell-mediated neointimal hyperplasia may occur separately from a macrophage-mediated mechanism.

Dataset Information

Monitoring the Remodeling of Biohybrid Tissue-Engineered Vascular Grafts by Multimodal Molecular Imaging.

Publications

Monitoring the Remodeling of Biohybrid Tissue-Engineered Vascular Grafts by Multimodal Molecular Imaging.

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