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基于酶法去除胶原和弹性蛋白成分对猪房室瓣前叶双轴力学响应的影响。

Effects of enzyme-based removal of collagen and elastin constituents on the biaxial mechanical responses of porcine atrioventricular heart valve anterior leaflets.

机构信息

Biomechanics and Biomaterials Design Laboratory, School of Aerospace and Mechanical Engineering, University of Oklahoma, USA.

Biomechanics and Biomaterials Design Laboratory, School of Aerospace and Mechanical Engineering, University of Oklahoma, USA; National Institute of Technology Rourkela, India.

出版信息

Acta Biomater. 2021 Nov;135:425-440. doi: 10.1016/j.actbio.2021.08.043. Epub 2021 Sep 2.

DOI:10.1016/j.actbio.2021.08.043
PMID:34481053
Abstract

The leaflets of the atrioventricular heart valves (AHVs) regulate the one-directional flow of blood through a coordination of the extracellular matrix components, including the collagen fibers, elastin, and glycosaminoglycans. Dysfunction of the AHVs, such as those caused by unfavorable microstructural remodeling, lead to valvular heart diseases and improper blood flow, which can ultimately cause heart failure. In order to better understand the mechanics and remodeling of the AHV leaflets and how therapeutics can inadvertently cause adverse microstructural changes, a systematic characterization of the role of each constituent in the biomechanical properties is appropriate. Previous studies have quantified the contributions of the individual microstructural components to tissue-level behavior for the semilunar valve cusps, but not for the AHV leaflets. In this study, for the first time, we quantify the relationships between microstructure and mechanics of the AHV leaflet using a three-step experimental procedure: (i) biaxial tension and stress relaxation testing of control (untreated) porcine AHV anterior leaflet specimens; (ii) enzyme treatment to remove a portion of either the collagen or elastin constituent; and (iii) biaxial tensile and stress relaxation testing of the constituent-removed (treated) specimens. We have observed that the removal of ∼100% elastin resulted in a ∼10% decrease in the tissue extensibility with biaxial tension and a ∼10% increase in the overall stress reduction with stress relaxation. In contrast, removal of 46% of the collagen content insignificantly affected tissue extensibility with biaxial tension and significantly increased stress decay (10%) with stress relaxation. These findings provide an insight into the microstructure-mechanics relationship of the AHVs and will be beneficial for future developments and refinements of microstructurally informed constitutive models for the simulation of diseased and surgically intervened AHV function. STATEMENT OF SIGNIFICANCE: This study presents, for the first time, a thorough mechanical characterization of the atrioventricular heart valve leaflets before and after enzymatic removal of elastin and collagen. We found that the biaxial tensile properties of elastin-deficient tissues and collagen-deficient are stiffer. The fact of elastin supporting low-stress valve function and collagen as the main load-bearing component was evident in a decrease in the low-tension modulus for elastin-deficient tissues and in the high-tension modulus for collagen-deficient tissues. Our quantification and experimental technique could be useful in predicting the disease-related changes in heart valve mechanics. The information obtained from this work is valuable for refining the constitutive models that describe the essential microstructure-mechanics relationship.

摘要

房室心脏瓣膜(AHV)的小叶调节着血液的单向流动,这是通过细胞外基质成分(包括胶原纤维、弹性蛋白和糖胺聚糖)的协调实现的。房室心脏瓣膜的功能障碍,如由于不利的微观结构重塑引起的功能障碍,会导致瓣膜性心脏病和血液流动不当,最终导致心力衰竭。为了更好地了解房室心脏瓣膜小叶的力学和重塑以及治疗方法如何无意中引起微观结构的不良变化,系统地表征每个成分在生物力学特性中的作用是合适的。先前的研究已经量化了各个微观结构成分对半新月瓣叶瓣组织水平行为的贡献,但没有量化房室心脏瓣膜小叶的贡献。在这项研究中,我们首次使用三步实验程序量化了房室心脏瓣膜小叶的微观结构和力学之间的关系:(i)对对照(未经处理)猪房室心脏前小叶标本进行双向拉伸和应力松弛测试;(ii)用酶处理去除一部分胶原或弹性蛋白成分;以及(iii)对去除成分(处理)的标本进行双向拉伸和应力松弛测试。我们观察到,去除约 100%的弹性蛋白会导致双向拉伸时组织延展性降低约 10%,应力松弛时整体应力降低约 10%。相比之下,去除 46%的胶原含量对双向拉伸时的组织延展性没有显著影响,但显著增加了应力松弛时的应力衰减(10%)。这些发现提供了对房室心脏瓣膜的微观结构-力学关系的深入了解,将有助于未来开发和改进基于微观结构的房室心脏瓣膜功能疾病和手术干预的本构模型。意义声明:本研究首次全面表征了酶法去除弹性蛋白和胶原前后房室心脏瓣膜小叶的力学特性。我们发现,缺乏弹性蛋白的组织的双向拉伸特性和缺乏胶原的组织的双向拉伸特性更硬。弹性蛋白支持低应力瓣膜功能,而胶原作为主要承载成分的事实,体现在缺乏弹性蛋白的组织的低张力模量降低和缺乏胶原的组织的高张力模量增加。我们的定量和实验技术可用于预测心脏瓣膜力学与疾病相关的变化。从这项工作中获得的信息对于改进描述基本微观结构-力学关系的本构模型是有价值的。

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