With respect to the limited lifespan of glutaraldehyde-treated bioprostheses (BHVs) 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 grafting detergent-based cell-depleted tissue engineered xenogeneic constructs are still controversial. Insufficient quantitative evaluations performed at preclinical level about the residual content of xenogeneic epitopes, detergents, and nucleic acid materials in such scaffolds have led to disappointing and disastrous results. The risk of these dramatic accidents reoccurring remains very high unless safety and reliable control tools aimed to reach their complete removal, in order to consider tissues biocompatible and suitable for clinical practice. 1. Introduction The increasing occurrence of heart valve insufficiency, following degenerative or rheumatic aetiology, represents a clinical burden with high social and economic relevance in worldwide population and requires as major resolution the surgical approach of valve substitution. Each year more than 290,000 patients go through valve replacement worldwide, and this number is projected to reach 850,000 by the year 2050, as the average age of the population increases [1, 2]. Actually commercialized biological heart valve prostheses (BHVs) ameliorated the natural history of the valve pathology, but their performance and endurance are limited in time. The interplay of multiple factors such as chemical interactions, surgical and mechanical factors, material fatigue [3], immunological and foreign body occurrences [4], and finally blood surface exposure leads to the replacement of BHVs after 8 to 10 years following the original implant. The limited lifespan of BHVs and availability of human tissue substitutes has led biomedical researchers to explore the use of animal donors as an attractive and unlimited source for biological devices (xenotransplantation) in the development of viable and functional tissue engineered construct for life-lasting prostheses. To ensure biocompatibility when implanting animal tissues into humans, it is mandatory to avoid hyperacute and acute rejection and vascular injury by removing the resident cellular component, antigens, and nucleic acids remnants. To meet these criteria, tissues are subjected to decellularization procedures combining the action of physical agents, detergents, enzymes, and
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