Decellularized tissue-engineered heart valves calcification: what do animal and clinical studies tell us?

Decellularized tissue-engineered heart valves calcification: what do animal and clinical studies tell us?
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DOI:
10.1007/s10856-020-06462-x
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发表时间:
2020-12-05
期刊:
Journal of materials science. Materials in medicine
影响因子:
--
通讯作者:
Mavrilas D
Mavrilas D
中科院分区:
其他
文献类型:
--
作者:
Badria AF;Koutsoukos PG;Mavrilas D

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心血管疾病是全世界的第一死因。在各种心脏功能障碍中,钙化引起的心脏瓣膜功能衰竭仍然是一个具有挑战性的问题。虽然药物依赖性治疗早期钙化可以减缓其进展,但心脏瓣膜置换术在晚期是不可避免的。目前,心脏瓣膜置换主要涉及两种类型的替代品:机械和生物心脏瓣膜。尽管它们在恢复心脏功能方面具有显着的优势,但从长远来看,这两种类型的瓣膜都存在严重的缺点。一方面,机械性组表现为非生理性血流动力学,需要长期抗凝治疗。另一方面,生物学检查显示钙化导致狭窄和/或返流。近年来,新的有前途的心脏瓣膜替代品出现了,称为脱细胞组织工程心脏瓣膜(dTEHV)。不同类型的脱细胞组织由于其上级的生物力学、生物相容性和仿生材料组成而在生物假体和组织工程瓣膜中被广泛测试。这样的优点允许成功的细胞附着、生长和功能,最终导致活的体内再生瓣膜组织。然而,还没有全面的研究涵盖dTEHV支架在钙化问题的效率方面的性能。在这篇综述文章中,我们试图回答脱细胞心脏瓣膜是否钙化的问题。还有,哪些因素使它们钙化,哪些因素降低和/或防止它们钙化。此外,与自体和人工生物心脏瓣膜中的钙化相比,综述讨论了dTEHV钙化的可能机制。为此,我们对所有已发表的脱细胞心脏瓣膜工作进行了回顾性研究。本综述仅包括动物和临床研究。根据去细胞化对钙化的影响,将这些动物和临床研究进一步细分为4类。由于心脏瓣膜钙化的复杂性,未纳入其他体外和计算机模拟研究。最后,我们比较了不同的结果,并总结了所有的坚实的发现,是否脱细胞心脏瓣膜钙化或没有。根据我们的综述,选择合适的心脏瓣膜组织来源(无免疫刺激残留物),脱细胞技术(无脱细胞组织的受损暴露残留物,无死细胞残留物,无脱细胞剂残留)和植入技术(避免手术植入过程中的钙化)可以提供完美的抗钙化潜力,即使没有体外细胞接种或额外的支架处理。
Cardiovascular diseases are the first cause of death worldwide. Among different heart malfunctions, heart valve failure due to calcification is still a challenging problem. While drug-dependent treatment for the early stage calcification could slow down its progression, heart valve replacement is inevitable in the late stages. Currently, heart valve replacements involve mainly two types of substitutes: mechanical and biological heart valves. Despite their significant advantages in restoring the cardiac function, both types of valves suffered from serious drawbacks in the long term. On the one hand, the mechanical one showed non-physiological hemodynamics and the need for the chronic anticoagulation therapy. On the other hand, the biological one showed stenosis and/or regurgitation due to calcification. Nowadays, new promising heart valve substitutes have emerged, known as decellularized tissue-engineered heart valves (dTEHV). Decellularized tissues of different types have been widely tested in bioprosthetic and tissue-engineered valves because of their superior biomechanics, biocompatibility, and biomimetic material composition. Such advantages allow successful cell attachment, growth and function leading finally to a living regenerative valvular tissue in vivo. Yet, there are no comprehensive studies that are covering the performance of dTEHV scaffolds in terms of their efficiency for the calcification problem. In this review article, we sought to answer the question of whether decellularized heart valves calcify or not. Also, which factors make them calcify and which ones lower and/or prevent their calcification. In addition, the review discussed the possible mechanisms for dTEHV calcification in comparison to the calcification in the native and bioprosthetic heart valves. For this purpose, we did a retrospective study for all the published work of decellularized heart valves. Only animal and clinical studies were included in this review. Those animal and clinical studies were further subcategorized into 4 categories for each depending on the effect of decellularization on calcification. Due to the complex nature of calcification in heart valves, other in vitro and in silico studies were not included. Finally, we compared the different results and summed up all the solid findings of whether decellularized heart valves calcify or not. Based on our review, the selection of the proper heart valve tissue sources (no immunological provoking residues), decellularization technique (no damaged exposed residues of the decellularized tissues, no remnants of dead cells, no remnants of decellularizing agents) and implantation techniques (avoiding suturing during the surgical implantation) could provide a perfect anticalcification potential even without in vitro cell seeding or additional scaffold treatment.
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