Aguiari Paola, Iop Laura, Favaretto Francesca, Fidalgo Cátia Marisa Lourenco, Naso Filippo, Milan Gabriella, Vindigni Vincenzo, Spina Michel, Bassetto Franco, Bagno Andrea, Vettor Roberto, Gerosa Gino
Department of Cardiac, Thoracic and Vascular Sciences, University of Padua, via Giustiniani 2, I-35128, Padua, Italy. Venetian Institute of Molecular Medicine, Padua, Italy.
Biomed Mater. 2017 Feb 3;12(1):015021. doi: 10.1088/1748-605X/aa5644.
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 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. 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.
尽管生物人工心脏瓣膜得到了广泛应用，但其耐久性有限（10 - 15年）。用化学交联剂如戊二醛处理生物组织会增加与生物人工瓣膜早期失效相关的结构退化风险。为克服现有解决方案的缺点，采用动物来源的脱细胞生物组织已成为一种有前景的方法。本研究旨在评估由采用新型TRITDOC（曲拉通X - 100和牛去氧胆酸）方法脱细胞的牛心包组成的体外心血管支架。通过组织学、生物分子、细胞、生化和生物力学分析评估了该处理的效果。TRITDOC方法可使牛心包支架完全脱细胞，同时保留细胞外基质结构和生物力学特性。通过一项专门的酶联免疫吸附测定试验已证明，TRITDOC方法可确保完全去除α - 半乳糖抗原，该抗原是导致异种生物材料超急性排斥和长期退化的原因。用人脂肪来源干细胞对脱细胞心包贴片进行静态接种，得到了均匀再填充的支架且无钙化迹象。将TRITDOC处理的牛心包的体外细胞/免疫相容性反应与从目前临床实践中使用的两种生物人工装置：PERIMOUNT MAGNA和TRIFECTA收集的经戊二醛处理的异种心包进行了比较。与测试的商用生物人工瓣膜相比，TRITDOC处理的牛心包表现出更低的补体激活、更低的细胞毒性以及更低的促炎细胞因子分泌倾向。因此，TRITDOC脱细胞心包可被视为生产人工心脏瓣膜的可能候选材料。
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