A novel decellularization protocol with cryopreservation of pulmonary allografts in an ovine model.

Objectives: Pulmonary allografts are commonly used for right ventricular outflow tract reconstruction. Cryopreserved allografts may develop degeneration and stenosis over time due to immune-related issues. Fresh decellularized aortic and pulmonary allografts have shown favourable early outcomes.

Advancing Heart Valve Replacement: Risk Mitigation of Decellularized Pulmonary Valve Preparation for Its Implementation in Public Tissue Banks.

Purpose: Cryopreserved homografts for valve replacement surgeries face a major problem regarding their durability after implantation and decellularized pulmonary heart valves have raised as potential new generation substitute for these surgeries. The present study aims to document the work performed for the safe implementation in public tissue banks of a new decellularization method for human pulmonary heart valves, based on previous risk evaluation.

Methods: After assessing new preparation method associated risks, using EuroGTP-II methodologies, an extensive array of in vitro were defined to validate the new technique, mitigate the risks and provide quality and safety data.

Aortic Valve Calcification Is Induced by the Loss of ALDH1A1 and Can Be Prevented by Agonists of Retinoic Acid Receptor Alpha: Preclinical Evidence for Drug Repositioning.

Background: To date, the only effective treatment of severe aortic stenosis is valve replacement. With the introduction of transcatheter aortic valve replacement and extending indications to younger patients, the use of bioprosthetic valves (BPVs) has considerably increased. The main inconvenience of BPVs is their limited durability because of mechanisms similar as the fibro-calcifying processes observed in native aortic stenosis.

Five-year results from a prospective, single-arm European trial on decellularized allografts for aortic valve replacement-the ARISE Study and ARISE Registry Data.

Objectives: Decellularized aortic homografts (DAH) were introduced as a new option for aortic valve replacement for young patients.

Methods: A prospective, EU-funded, single-arm, multicentre study in 8 centres evaluating non-cryopreserved DAH for aortic valve replacement.

Results: A total of 144 patients (99 male) were prospectively enrolled in the ARISE Trial between October 2015 and October 2018 with a median age of 30.

Paediatric aortic valve replacement using decellularized allografts: a multicentre update following 143 implantations and five-year mean follow-up.

Objectives: Decellularized aortic homografts (DAH) were introduced in 2008 as a further option for paediatric aortic valve replacement (AVR).

Methods: Prospective, multicentre follow-up of all paediatric patients receiving DAH for AVR in 8 European centres.

Results: A total of 143 DAH were implanted between February 2008 and February 2023 in 137 children (106 male, 74%) with a median age of 10.

A latent cardiomyocyte regeneration potential in human heart disease.

Cardiomyocytes in the adult human heart show a regenerative capacity, with an annual renewal rate around 0.5%. Whether this regenerative capacity of human cardiomyocytes is employed in heart failure has been controversial.

Advantages and challenges in processing and quality control of decellularized heart valves.

More than 1000 donated aortic and pulmonary valves from predominantly European tissue banks were centrally decellularized and delivered to hospitals in Europe and Japan. Here, we report on the processing and quality controls before, during and after the decellularization of these allografts. Our experiences show that all tissue establishments, which provide native cardiovascular allografts for decellularization, meet comparably high-quality standards, regardless of their national origin.

Matched comparison of decellularized homografts and bovine jugular vein conduits for pulmonary valve replacement in congenital heart disease.

For decades, bovine jugular vein conduits (BJV) and classic cryopreserved homografts have been the two most widely used options for pulmonary valve replacement (PVR) in congenital heart disease. More recently, decellularized pulmonary homografts (DPH) have provided an alternative avenue for PVR. Matched comparison of patients who received DPH for PVR with patients who received bovine jugular vein conduits (BJV) considering patient age group, type of heart defect, and previous procedures.

Vascular allografts for clinical application in Europe: assessment of 30 years of experience with vascular tissue banking in Brussels.

Vascular tissue banking has been carried out in Brussels for over 30 years in compliance with EU and Swiss tissue banking regulations. A total of 2.765 vascular tissue donations were performed in Belgian, French, Netherlands and Suisse transplant centres: 547(20%), 1.

Modulation of inflammatory M1-macrophages phenotype by valvular interstitial cells.

Background: Aortic valve stenosis involves inflammation, excess deposition of a collagen-rich extracellular matrix, and calcification. Recent studies have shown that M1 or inflammatory macrophages derived from infiltrating monocytes promote calcification of valvular interstitial cells, the most prevalent cell type of the aortic valve. We hypothesized that valvular interstitial cells could modulate inflammatory macrophages phenotype.

Serial assessment of early antibody binding to decellularized valved allografts.

Objectives: Decellularized homograft valves (DHV) appear to elicit an immune response despite efficient donor cell removal.

Materials And Methods: A semiquantitative Dot-Blot analysis for preformed and new recipient antibodies was carried out in 20 patients following DHV implantation on days 0, 1, 7, and 28 using secondary antihuman antibodies. Immune reactions were tested against the implanted DHV as well as against the stored samples of 5 non-implanted decellularized aortic (DAH) and 6 pulmonary homografts (DPH).

Alterations in Human Mitral Valve Mechanical Properties Secondary to Left Ventricular Remodeling: A Biaxial Mechanical Study.

Secondary mitral regurgitation occurs when a left ventricular problem causes leaking of the mitral valve. The altered left ventricular geometry changes the orientation of the subvalvular apparatus, thereby affecting the mechanical stress on the mitral valve. This in turn leads to active remodeling of the mitral valve, in order to compensate for the ventricular remodeling.

5-Year results from the prospective European multi-centre study on decellularized homografts for pulmonary valve replacement ESPOIR Trial and ESPOIR Registry data.

Objectives: Early results from the prospective ESPOIR Trial have indicated excellent results for pulmonary valve replacement using decellularized pulmonary homografts (DPH).

Methods: A 5-year analysis of ESPOIR Trial patients was performed to provide an insight into the midterm DPH performance. ESPOIR Trial and Registry patients were matched with cryopreserved homografts (CH) patients considering patient age, type of heart defect and previous procedures to present the overall experience with DPH.

Residual immune response towards decellularized homografts may be highly individual.

Objectives: Decellularized homograft valves (DHVs) have shown promising clinical results, particularly in the treatment of congenital heart disease. However, DHV appears to elicit an immune response in a subset of young patients, indicated by early valve degeneration. As the decellularization process is quality controlled for each DHV, we hypothesized that there may be residual immunogenicity within the extracellular matrix of DHV.

An Model to Study Endothelialization of Cardiac Graft Tissues Under Flow.

Pulmonary valve replacement is performed with excellent resultant hemodynamics in patients that have underlying congenital or acquired heart valve defects. Despite recent advancements in right ventricular outflow tract reconstruction, an increased risk of developing infective endocarditis remains, which has a more common occurrence for conduits of bovine jugular vein (BJV) origin compared with cryopreserved homografts. The reason for this is unclear although it is hypothesized to be associated with an aberrant phenotypic state of cells that reendothelialize the graft tissue postimplantation.

Transplantation of cryopreserved human heart valves in Europe: 30 years of banking in Brussels and future perspectives.

For over 30 years, our TE has processed, controlled for quality and distributed cryopreserved allograft valves for human application. We present a review of this activity and future perspectives of cardiovascular tissue banking. The donor age and medical/behavioral history are in compliance with the regulations of the EUMS.

The BD BACTEC FX blood culture system with the gentlemacs dissociator is suitable for sterility testing of heart valve and vascular allografts-A validation study.

To present our validation study of the BD BACTEC FX blood culture system for sterility testing of cardiovascular tissues aimed for human application. For operational qualification, we performed temperature mapping of the system, vacuum test using non-inoculated BACTEC vials, and growth promotion tests by injecting contaminant strains into aerobic and anaerobic bottles. For performance qualification, negative control, assessment of method suitability, evaluation of sensitivity limits, control of neutralization of antibiotics in biopsy samples from allografts and tissue toxicity effects, were performed.

Human Aortic Valve Interstitial Cells Display Proangiogenic Properties During Calcific Aortic Valve Disease.

Objective: The study's aim was to analyze the capacity of human valve interstitial cells (VICs) to participate in aortic valve angiogenesis. Approach and Results: VICs were isolated from human aortic valves obtained after surgery for calcific aortic valve disease and from normal aortic valves unsuitable for grafting (control VICs). We examined VIC in vitro and in vivo potential to differentiate in endothelial and perivascular lineages.

adheres avidly to decellularised cardiac homograft tissue in vitro in the fibrinogen-dependent manner.

Objective: Infective endocarditis remains a severe complication associated with a high morbidity and mortality in patients after heart valve replacement. Exploration of the pathogenesis is of high demand and we, therefore, present a competent model that allows studying bacterial adherence and the role of plasma fibrinogen in this process using a new in-house designed low-volume flow chamber. Three cardiac graft tissues used for pulmonary valve replacement have been tested under shear conditions to investigate the impact of surface composition on the adhesion events.

The time has come to extend the expiration limit of cryopreserved allograft heart valves.

Despite the wide choice of commercial heart valve prostheses, cryopreserved semilunar allograft heart valves (C-AHV) are required, and successfully transplanted in selected groups of patients. The expiration limit (EL) criteria have not been defined yet. Most Tissue Establishments (TE) use the EL of 5 years.

Paediatric aortic valve replacement using decellularized allografts.

Objectives: Options for paediatric aortic valve replacement (AVR) are limited if valve repair is not feasible. Results of paediatric Ross procedures are inferior to adult Ross results, and mechanical AVR imposes constant anticoagulation with the inherent risks.

Methods: The study design was a prospective, multicentre follow-up of all paediatric patients receiving decellularized aortic homografts (DAHs) for AVR in 8 European centres.