Decellularized pig pulmonary heart valves—Depletion of nucleic acids measured by proviral PERV pol (original) (raw)
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Strategies for development of decellularized heart valve scaffolds for tissue engineering
Biomaterials, 2022
Valvular heart diseases (VHDs) are currently treated using either mechanical or bioprosthetic heart valves. Unfortunately, mechanical valves require lifelong anticoagulation therapy, and bioprosthetic valves calcify and degrade over time, requiring subsequent valve replacement surgeries. Besides, both valves cannot grow with patients. Heart valve tissue engineering uses scaffolds as valve replacements with the potential to grow with patents, function indefinitely, and not require anticoagulation medication. These scaffolds provide threedimensional supports for cellular adhesion and growth, leading to tissue formation and, finally, a new functional heart valve development. Heart valve scaffolds are made of either polymeric materials or decellularized tissue obtained from allogeneic or xenogeneic sources. This review discusses processes for preparing decellularized heart valve scaffolds, including decellularization, crosslinking, surface-coating, and sterilization. We also examine the predominant issues in scaffold development. Further, decellularized heart valve scaffold function in vitro and in vivo is evaluated.
Off-the-shelf human decellularized tissue-engineered heart valves in a non-human primate model
Biomaterials, 2013
Preclinical in vivo model Minimally invasive Homologous valve replacement a b s t r a c t Heart valve tissue engineering based on decellularized xenogenic or allogenic starter matrices has shown promising first clinical results. However, the availability of healthy homologous donor valves is limited and xenogenic materials are associated with infectious and immunologic risks. To address such limitations, biodegradable synthetic materials have been successfully used for the creation of living autologous tissueengineered heart valves (TEHVs) in vitro. Since these classical tissue engineering technologies necessitate substantial infrastructure and logistics, we recently introduced decellularized TEHVs (dTEHVs), based on biodegradable synthetic materials and vascular-derived cells, and successfully created a potential off-theshelf starter matrix for guided tissue regeneration. Here, we investigate the host repopulation capacity of such dTEHVs in a non-human primate model with up to 8 weeks follow-up. After minimally invasive delivery into the orthotopic pulmonary position, dTEHVs revealed mobile and thin leaflets after 8 weeks of follow-up. Furthermore, mild-moderate valvular insufficiency and relative leaflet shortening were detected. However, in comparison to the decellularized human native heart valve control e representing currently used homografts e dTEHVs showed remarkable rapid cellular repopulation. Given this substantial in situ remodeling capacity, these results suggest that human cell-derived bioengineered decellularized materials represent a promising and clinically relevant starter matrix for heart valve tissue engineering. These biomaterials may ultimately overcome the limitations of currently used valve replacements by providing homologous, non-immunogenic, off-the-shelf replacement constructs.
MODERN DECELLULARIZATION SCAFFOLD FRAMING FROM PORCINE HEART VALVE
Tissue engineering heart valve is a novel experimental concept to develop ideal heart valve substitutes. Conventional mechanical valve used for replacement require the anti-coagulation therapy which decreases quality of life. Now a days bioprosthetic heart valve replacement are either of animal origin such as porcine pulmonary or aortic valves and bovine pericardial valves or taken from human donors. But both were having lifelong anticoagulation therapy associated with a substantial risk of spontaneous bleeding and embolism. Further these valves lack in growth potential in general. The new methodologies for a decellularization of porcine pulmonary and aortic valves were generated from porcine pulmonary. In this aortic valves were decellularized by deterging cell extraction using sodium dodecyl sulfate and dimethyl sulfoxide. Further analysis of decellularization were performed by Hematoxylin-and-Eosin (stain) and 4',6-diamidino-2-phenylindole (stain). The decellularization method shows the complete removal of the original cells from the scaffolds. Thus porcine pulmonary, aortic valves were completely decellularized by detergent extraction procedure
Biomedical materials (Bristol, England), 2017
Notwithstanding their wide exploitation, biological prosthetic heart valves are characterized by limited durability (10-15 years). The treatment of biological tissues with chemical crosslinking agents such as glutaraldehyde accounts for the enhanced risk of structural deterioration associated with the early failure of bioprosthetic valves. To overcome the shortcomings of the currently available solutions, adoption of decellularized biological tissues of animal origin has emerged as a promising approach. The present study aims to assess in vitro cardiovascular scaffolds composed of bovine pericardium decellularized with the novel TRITDOC (TRIton-X100 and TauroDeOxyCholic acid) procedure. The effects of the treatment have been assessed by means of histological, biomolecular, cellular, biochemical and biomechanical analyses. The TRITDOC procedure grants the complete decellularization of bovine pericardial scaffolds while preserving the extracellular matrix architecture and the biomecha...
Biocompatibility Features of Heart Valve Bioprosthetic Devices
Conference Papers in Science , 2014
With respect to the limited lifespan of glutaraldehyde(GA)- treated bioprostheses to date there is almost no alternative when heart valve replacement surgery is required and most advanced current research attempts to develop tissue engineered valve scaffolds to be implanted in vivo or after in vitro preconditioning and dynamic seeding with host cells. However the clinical outcomes of detergent-based cell-depleted tissue engineered xenogeneic constructs are still controversial. Therefore, we investigated whether the clinical drawbacks of GA-treated and decellularized bioprosthetic devices might be related to residual xenogenic epitope and/or to biocompatibility problems associated with by-produts of the detergent-based decellularizing process. Accordingly we determined the residual content of detergents and that of residual xenogenic antigens in both GAtreated and detergent-based preparations (five different procedures). The presence of residual detergents was detected in all the res...
The increasing urgency for replacement of pathological heart valves is a major stimulus for research on alternatives to glutaraldehyde-treated grafts. New xenogeneic acellular heart valve substitutes that can be repopulated by host cells are currently under investigation. Anionic surfactants, including bile acids, have been widely used to eliminate the resident cell components chiefly responsible for the immunogenicity of the tissue, even if detergent toxicity might present limitations to the survival and/or functional expression of the repopulating cells. To date, the determination of residual detergent has been carried out almost exclusively on the washings following cell removal procedures. Here, a novel HPLC-based procedure is proposed for the direct quantification of detergent (cholate, deoxycholate, and taurodeoxycholate) residues entrapped in the scaffold of decellularized porcine aortic and pulmonary valves. The method was demonstrated to be sensitive, reproducible, and extendable to different types of detergent. This assessment also revealed that cell-depleted heart valve scaffolds prepared according to procedures currently considered for clinical use might contain significant amount of surfactant.
Polymers, 2022
The most common aortic valve diseases in adults are stenosis due to calcification and regurgitation. In pediatric patients, aortic pathologies are less common. When a native valve is surgically replaced by a prosthetic one, it is necessary to consider that the latter has a limited durability. In particular, current bioprosthetic valves have to be replaced after approximately 10 years; mechanical prostheses are more durable but require the administration of permanent anticoagulant therapy. With regard to pediatric patients, both mechanical and biological prosthetic valves have to be replaced due to their inability to follow patients’ growth. An alternative surgical substitute can be represented by the acellular porcine aortic valve that exhibits less immunogenic risk and a longer lifespan. In the present study, an efficient protocol for the removal of cells by using detergents, enzyme inhibitors, and hyper- and hypotonic shocks is reported. A new detergent (Tergitol) was applied to r...
Biomedical Materials, 2017
Notwithstanding their wide exploitation, biological prosthetic heart valves are characterized by limited durability (10-15 years). The treatment of biological tissues with chemical crosslinking agents such as glutaraldehyde accounts for the enhanced risk of structural deterioration associated with the early failure of bioprosthetic valves. To overcome the shortcomings of the currently available solutions, adoption of decellularized biological tissues of animal origin has emerged as a promising approach. The present study aims to assessin vitro cardiovascular scaffolds composed of bovine pericardium decellularized with the novel TRITDOC (TRIton-X100 and TauroDeOxyCholic acid) procedure. The effects of the treatment have been assessed by means of histological, biomolecular, cellular, biochemical and biomechanical analyses. The TRITDOC procedure grants the complete decellularization of bovine pericardial scaffolds while preserving the extracellular matrix architecture and the biomechanical properties. With a dedicated ELISA test, the TRITDOC procedure has been proven to ensure the complete removal of the alphaGal antigen, responsible for hyperacute rejection and for long-term deterioration of xenogenic biomaterials. Static seeding of the acellular pericardial patches with human adipose-derived stem cells resulted in an evenly repopulated scaffold without signs of calcification. The in vitro cyto-/immuno-compatibility response of the TRITDOC-bovine pericardium was compared with glutaraldehyde-treated xenogenic pericardium collected from two bioprosthetic devices currently used in clinical practice: PERIMOUNT MAGNA and TRIFECTA TM. TRITDOC-bovine pericardium exhibited lower complement activation, lower cytotoxicity and a lower tendency to secrete pro-inflammatory cytokines compared to the tested commercial bioprostheses. Therefore, TRITDOC-decellularized pericardium could be considered as possible candidate material for the production of prosthetic heart valves. Abbreviations GA glutaraldehyde ECM extracellular matrix NBP native bovine pericardium TBP TRITDOC-decellularized bovine pericardium TBP-GA TRITDOC-decellularized bovine pericardium treated with GA RECEIVED
Xenotransplantation, 2020
The use of decellularized xenogeneic heart valves might offer a solution to overcome the issue of human valve shortage. The aim of this study was to revise decellularization protocols in combination with enzymatic deglycosylation, in order to reduce the immunogenicity of porcine pulmonary heart valves, in means of cells, carbohydrates, and, primarily, Galα1‐3Gal (α‐Gal) epitope removal. In particular, the valves were decellularized with sodium dodecylsulfate/sodium deoxycholate (SDS/SD), Triton X‐100 + SDS (Tx + SDS), or Trypsin + Triton X‐100 (Tryp + Tx) followed by enzymatic digestion with PNGaseF, Endoglycosidase H, or O‐glycosidase combined with Neuraminidase. Results showed that decellularization alone reduced carbohydrate structures only to a limited extent, and it did not result in an α‐Gal free scaffold. Nevertheless, decellularization with Tryp + Tx represented the most effective decellularization protocol in means of carbohydrates reduction. Overall, carbohydrates and α‐Ga...
Romanian Journal of Cardiology, 2021
Well documented shortcomings of current heart valve substitutes – biological and mechanical prostheses make them imperfect choices for patients diagnosed with heart valve disease, in need for a cardiac valve replacement. Regenerative Medicine and Tissue Engineering represent the research grounds of the next generation of valvular prostheses – Tissue Engineering Heart Valves (TEHV). Mimicking the structure and function of the native valves, TEHVs are three dimensional structures obtained in laboratories encompassing scaffolds (natural and synthetic), cells (stem cells and differentiated cells) and bioreactors. The literature stipulates two major heart valve regeneration paradigms, differing in the manner of autologous cells repopulation of the scaffolds; in vitro, or in vivo, respectively. During the past two decades, multidisciplinary both in vitro and in vitro research work was performed and published. In vivo experience comprises preclinical tests in experimental animal model and ...