Impact of γ-Irradiation on Extracellular Matrix of Porcine Pulmonary Valves

Sarathchandra, Padmini; Smolenski, Ryszard T.; Yuen, Ada H. Y.; Chester, Adrian H.; Goldstein, Steven A.; Heacox, Albert E.; Yacoub, Magdi H.; Taylor, Patricia M.

doi:10.1016/j.jss.2011.10.011

Cited by 18 publications

(16 citation statements)

References 24 publications

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“…The decision to adopt this approach was based on preliminary studies that showed that treatment of the decellularized valves with peracetic acid ablated collagen IV immunostaining in the basement membrane, and knowledge that irradiation sterilization is not considered appropriate for valve allografts due to the potential for causing deterioration in ECM properties and clinical performance (Helder et al ., 2016; Sarathchandra et al ., 2012). Until a reliable sterilization process that does not adversely affect the ECM is demonstrated for biological tissue grafts, it remains acceptable to adopt aseptic production for human tissue products.…”

Section: Discussionmentioning

confidence: 99%

Decellularization of human donor aortic and pulmonary valved conduits using low concentration sodium dodecyl sulfate

Vafaee

Thomas

Desai

et al. 2017

J Tissue Eng Regen Med

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The clinical use of decellularized cardiac valve allografts is increasing. Long‐term data will be required to determine whether they outperform conventional cryopreserved allografts. Valves decellularized using different processes may show varied long‐term outcomes. It is therefore important to understand the effects of specific decellularization technologies on the characteristics of donor heart valves. Human cryopreserved aortic and pulmonary valved conduits were decellularized using hypotonic buffer, 0.1% (w/v) sodium dodecyl sulfate and nuclease digestion. The decellularized tissues were compared to cellular cryopreserved valve tissues using histology, immunohistochemistry, quantitation of total deoxyribose nucleic acid, collagen and glycosaminoglycan content, in vitro cytotoxicity assays, uniaxial tensile testing and subcutaneous implantation in mice. The decellularized tissues showed no histological evidence of cells or cell remnants and >97% deoxyribose nucleic acid removal in all regions (arterial wall, muscle, leaflet and junction). The decellularized tissues retained collagen IV and von Willebrand factor staining with some loss of fibronectin, laminin and chondroitin sulfate staining. There was an absence of major histocompatibility complex Class I staining in decellularized pulmonary valve tissues, with only residual staining in isolated areas of decellularized aortic valve tissues. The collagen content of the tissues was not decreased following decellularization however the glycosaminoglycan content was reduced. Only moderate changes in the maximum load to failure of the tissues were recorded postdecellularization. The decellularized tissues were noncytotoxic in vitro, and were biocompatible in vivo in a mouse subcutaneous implant model. The decellularization process will now be translated into a good manufacturing practices‐compatible process for donor cryopreserved valves with a view to future clinical use. Copyright © 2016 The Authors Tissue Engineering and Regenerative Medicine published by John Wiley & Sons, Ltd.

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Section: Discussionmentioning

confidence: 99%

Decellularization of human donor aortic and pulmonary valved conduits using low concentration sodium dodecyl sulfate

Vafaee

Thomas

Desai

et al. 2017

J Tissue Eng Regen Med

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“…In that study, irradiation was found to cause “a marked reduction in the expression of collagen types I and III, hyaluronan, chondroitan 6-sulphate, and versican” compared to native heart valves or heart valves undergoing only decellularization (Sarathchandra et al, 2012). Irradiation also increased the spacing between collagen fibrils and decreased the density of pyridinoline collagen cross-links compared to controls, suggesting additional disruption of the ECM (Sarathchandra et al, 2012). In a separate study of the effect of gamma-irradiation on porcine heart valves, a protocol consisting of immersing the valves in 80% polythethylene glycol followed by irradiation resulted in no change in maximum load, collagen content, or histologic appearance of the ECM compared to controls (Ota et al, 2007).…”

Section: Effects Of Antigen Removal Protocols On Tissue Biomechanicalmentioning

confidence: 99%

“…Physical treatments such as freezing and thawing, sonication, and gamma irradiation or photo-oxidation are used to disrupt the cells within a tissue and are typically used in conjunction with a chemical treatment that facilitates removal of the cell components. Gamma irradiation and photo-oxidation both act to cross-link proteins within a tissue and have been examined as sole treatments or in combination with other antigen removal methods (Akens et al, 2002; Akens et al, 2001; Ota et al, 2007; Sarathchandra et al, 2012). The goal of an antigen removal protocol should be to target removal of antigens that trigger an immune response without disrupting the important structural molecules that lend a tissue its mechanical properties.…”

Section: Decellularization and Antigen Removal From Xenogeneic Tissuesmentioning

confidence: 99%

Section: Effects Of Antigen Removal Protocols On Tissue Biomechanicalmentioning

confidence: 99%

“…Gamma-irradiation has been performed as an adjunct to decellularization of porcine heart valves using a hypotonic solution (Sarathchandra et al, 2012). In that study, irradiation was found to cause “a marked reduction in the expression of collagen types I and III, hyaluronan, chondroitan 6-sulphate, and versican” compared to native heart valves or heart valves undergoing only decellularization (Sarathchandra et al, 2012). Irradiation also increased the spacing between collagen fibrils and decreased the density of pyridinoline collagen cross-links compared to controls, suggesting additional disruption of the ECM (Sarathchandra et al, 2012).…”

Section: Effects Of Antigen Removal Protocols On Tissue Biomechanicalmentioning

confidence: 99%

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Antigen removal for the production of biomechanically functional, xenogeneic tissue grafts

Cissell

Griffiths

et al. 2014

Journal of Biomechanics

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Xenogeneic tissues are derived from other animal species and provide a source of material for engineering mechanically functional tissue grafts, such as heart valves, tendons, ligaments, and cartilage. Xenogeneic tissues, however, contain molecules, known as antigens, which invoke an immune reaction following implantation into a patient. Therefore, it is necessary to remove the antigens from a xenogeneic tissue to prevent immune rejection of the graft. Antigen removal can be accomplished by treating a tissue with solutions and/or physical processes that disrupt cells and solubilize, degrade, or mask antigens. However, processes used for cell and antigen removal from tissues often have deleterious effects on the extracellular matrix (ECM) of the tissue, rendering the tissue unsuitable for implantation due to poor mechanical properties. Thus, the goal of an antigen removal process should be to reduce the antigen content of a xenogeneic tissue while preserving its mechanical functionality. To expand the clinical use of antigen-removed xenogeneic tissues as biomechanically functional grafts, it is essential that researchers examine tissue antigen content, ECM composition and architecture, and mechanical properties as new antigen removal processes are developed.

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Advances in xenogeneic donor decellularized organs: A review on studies with sheep and porcine‐derived heart valves

Inal,

Avci,

Hassan

et al. 2024

Bioengineering & Transla Med

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Heart valve replacement surgeries are performed on patients suffering from abnormal heart valve function. In these operations, the problematic tissue is replaced with mechanical valves or with bioprosthetics that are being developed. The thrombotic effect of mechanical valves, reflecting the need for lifelong use of anticoagulation drugs, and the short‐lived nature of biological valves make these two types of valves problematic. In addition, they cannot adapt to the somatic growth of young patients. Although decellularized scaffolds have shown some promise, a successful translation has so far evaded. Although decellularized porcine xenografts have been extensively studied in the literature, they have several disadvantages, such as a propensity for calcification in the implant model, a risk of porcine endogenous retrovirus (PERV) infection, and a high xenoantigen density. As seen in clinical data, it is clear that there are biocompatibility problems in almost all studies. However, since decellularized sheep heart valves have not been tried in the clinic, a large data pool could not be established. This review compares and contrasts decellularized porcine and sheep xenografts for heart valve tissue engineering. It reveals that decellularized sheep heart valves can be an alternative to pigs in terms of biocompatibility. In addition, it highlights the potential advantages of bioinks derived from the decellularized extracellular matrix in 3D bioprinting technology, emphasizing that they can be a new alternative for the application. We also outline the future prospects of using sheep xenografts for heart valve tissue engineering.

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Impact of γ-Irradiation on Extracellular Matrix of Porcine Pulmonary Valves

Cited by 18 publications

References 24 publications

Decellularization of human donor aortic and pulmonary valved conduits using low concentration sodium dodecyl sulfate

Decellularization of human donor aortic and pulmonary valved conduits using low concentration sodium dodecyl sulfate

Antigen removal for the production of biomechanically functional, xenogeneic tissue grafts

Advances in xenogeneic donor decellularized organs: A review on studies with sheep and porcine‐derived heart valves

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