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 ofαvβ3integrins 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.
6 October 2022 in Tissue Engineering and Regenerative Medicine
Background: The production of tissue-engineered vascular graft (TEVG) usually involves a prolonged bioreactor cultivation period of up to several weeks to achieve maturation of extracellular matrix and sufficient mechanical strength. Therefore, we aimed to substantially shorten this conditioning time by combining a TEVG textile scaffold with a recently developed copolymer reinforced fibrin gel as a cell carrier. We further implemented our grafts with magnetic resonance imaging (MRI) contrast agents to allow thein-vitromonitoring of the TEVG’s remodeling process.Methods: Biodegradable polylactic-co-glycolic acid (PLGA) was electrospun onto a non-degradable polyvinylidene fluoride scaffold and molded along with copolymer-reinforced fibrin hydrogel and human arterial cells. Mechanical tests on the TEVGs were performed both instantly after molding and 4 days of bioreactor conditioning. The non-invasivein vitromonitoring of the PLGA degradation and the novel imaging of fluorinated thermoplastic polyurethane (19F-TPU) were performed using 7T MRI.Results: After 4 days of close loop bioreactor conditioning, 617 ± 85 mmHg of burst pressure was achieved, and advanced maturation of extracellular matrix (ECM) was observed by immunohistology, especially in regards to collagen and smooth muscle actin. The suture retention strength (2.24 ± 0.3 N) and axial tensile strength (2.45 ± 0.58 MPa) of the TEVGs achieved higher values than the native arteries used as control. The contrast agents labeling of the TEVGs allowed the monitorability of the PLGA degradation and enabled the visibility of the non-degradable textile component.Conclusion: Here, we present a concept for a novel textile-reinforced TEVG, which is successfully produced in 4 days of bioreactor conditioning, characterized by increased ECM maturation and sufficient mechanical strength. Additionally, the combination of our approach with non-invasive imaging provides further insights into TEVG’s clinical application.
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 α-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.
22 October 2024 in Annals of Biomedical Engineering
The development of cardiovascular implants is abundant, yet their clinical adoption remains a significant challenge in the treatment of valvular diseases. Tissue-engineered heart valves (TEHV) have emerged as a promising solution due to their remodeling capabilities, which have been extensively studied in recent years. However, ensuring reproducible production and clinical translation of TEHV requires robust longitudinal monitoring methods. Cardiovascular magnetic resonance imaging (MRI) is a non-invasive, radiation-free technique providing detailed valvular imaging and functional assessment. To facilitate this, we designed a state-of-the-art metal-free bioreactor enabling dynamic MRI and ultrasound imaging. Our compact bioreactor, tailored to fit a 72 mm bore 7 T MRI coil, features an integrated backflow design ensuring MRI compatibility. A pneumatic drive system operates the bioreactor, minimizing potential MRI interference. The bioreactor was digitally designed and constructed using polymethyl methacrylate, utilizing only polyether ether ketone screws for secure fastening. Our biohybrid TEHV incorporates a non-degradable polyethylene terephthalate textile scaffold with fibrin matrix hydrogel and human arterial smooth muscle cells. As a result, the bioreactor was successfully proven to be MRI compatible, with no blooming artifacts detected. The dynamic movement of the TEHVs was observed using gated MRI motion artifact compensation and ultrasound imaging techniques. In addition, the conditioning of TEHVs in the bioreactor enhanced ECM production. Immunohistology demonstrated abundant collagen, α-smooth muscle actin, and a monolayer of endothelial cells throughout the valve cusp. Our innovative methodology provides a physiologically relevant environment for TEHV conditioning and development, enabling accurate monitoring and assessment of functionality, thus accelerating clinical acceptance.
Thoracoabdominal aortic aneurysms (TAAAs) are uncommon and usually silent until rupture, causing a substantial burden to the health care system. Aneurysm growth and rupture prediction is mainly based on aneurysm diameter measurement by imaging modalities, meaning that the biology of aneurysm growth is not part of a potentially more adequate surveillance of aortic aneurysm patients. Alternatives or complementary options for aortic aneurysm surveillance are an ongoing, non-addressed open issue of vascular medicine. The application of different biomarkers has been discussed, yet so far, an adequate candidate for aortic aneurysm surveillance, if it comes to the thoracic or thoracoabdominal aorta, preferably without radiation exposure, has not been named. Elastin breakdown, as a component of aortic wall degeneration primarily driven by matrix metalloproteinases (MMPs), is a core element of aneurysm development. Desmosine is an elastin-specific cross-link increasingly studied as a circulating or urinary biomarker of compromised aortic wall integrity and disease activity. Accordingly, this review investigated whether plasma desmosine (pDES), a highly specific marker of elastin degradation, could be used as a non-invasive biomarker for detecting aortic aneurysms and assessing their risk profile. The existing literature of desmosine in fields of aortic pathologies in the acute and chronic setting will be assessed based on the current literature; furthermore, future perspectives of desmosine as a biomarker of aortic pathologies, such as aortic aneurysm dynamics, will be discussed.
Background/Objectives: Arterial wall compliance is a key biomechanical property influencing local hemodynamics, vascular remodeling, and surgical performance. Despite its clinical relevance, reference values in lower limb arteries remain insufficiently characterized. This systematic review and meta-analysis aimed to synthesize existing evidence on cross-sectional compliance (CC) of the common femoral artery (CFA), superficial femoral artery (SFA), and popliteal artery (PA) in healthy adults. Methods: A systematic literature search was performed according to PRISMA guidelines to identify studies reporting arterial wall compliance in healthy adults. Study characteristics, measurement techniques, and compliance values were extracted. Risk of bias was assessed using a QUADAS-2/COSMIN-based tool. Pooled estimates were calculated using random effects meta-analysis, PROSPERO CRD420251208399. Results: Thirty-four studies with a total of 3452 participants were included. Reported compliance values varied substantially. The pooled mean CC of the CFA was 0.95 (95%-CI 0.83–1.06, I2 = 99.2%). Sex-specific analysis showed a pooled mean CC of 1.07 (95%-CI 0.87–1.28, I2 = 99.0%) in males and 0.90 (95%-CI 0.75–1.05, I2 = 83.6%) in females. Meta-regression of age, sex, and BMI did not significantly demonstrate association between these moderators and CC or explain observed heterogeneity. Extracted CC values of the SFA ranged from 0.17 to 0.50 mm2/kPa, and mean CC values of the PA ranged from 0.44 to 0.62 mm2/kPa. Conclusions: Available data on CC in lower limb arteries are limited and heterogeneous. Given the substantial between-study heterogeneity, the pooled estimates resulting from the meta-analysis should therefore be considered descriptive and should not be interpreted as definitive physiological reference values.