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纳米升温辅助玻璃化冷冻复苏过程中人心和鼠心模型的热机械应力分析。

Thermomechanical stress analyses of nanowarming-assisted recovery from cryopreservation by vitrification in human heart and rat heart models.

机构信息

Department of Mechanical Engineering, Biothermal Technology Laboratory, Carnegie Mellon University, Pittsburgh, PA, United States of America.

Department of Mechanical Engineering, Forbes Avenue, Pittsburgh, PA, United States of America.

出版信息

PLoS One. 2023 Aug 16;18(8):e0290063. doi: 10.1371/journal.pone.0290063. eCollection 2023.

Abstract

This study investigates thermomechanical stress in cryopreservation by vitrification of the heart, while exploring the effects of nanowarming-assisted recovery from cryogenic storage. This study expands upon a recently published study, combining experimental investigation and thermal analysis of cryopreservation on a rat heart model. Specifically, this study focuses on scenarios with variable concentrations of silica-coated iron-oxide nanoparticles (sIONPs), while accounting for loading limitations associated with the heart physiology, as well as the properties of cryoprotective agent (CPA) solution and the geometry of the container. Results of this study suggest that variable sIONP concentration based on the heart physiology will elevate mechanical stresses when compared with the mathematically simplified, uniform distribution case. The most dangerous part of rewarming is below glass transition and at the onset of nanowarming past the glass transition temperature on the way for organ recovery from cryogenic storage. Throughout rewarming, regions that rewarm faster, such as the chambers of the heart (higher sIONP concentration), undergo compressive stresses, while the slower rewarming regions, such as the heart myocardium (low sIONP concentration), undergo tension. Being a brittle material, the vitrified organ is expected to fail under tension in lower stresses than in compression. Unfortunately, the location and magnitude of the maximum stress in the investigated cases varied, while general rules were not identified. This investigation demonstrates the need to tailor the thermal protocol of heart cryopreservation on a case-by-case basis, since the location, orientation, magnitude, and instant at which the maximum mechanical stress is found cannot be predicted a priori. While thermomechanical stress poses a significant risk to organ integrity, careful design of the thermal protocol can be instrumental in reducing the likelihood of structural damage, while taking full advantage of the benefits of nanowarming.

摘要

本研究通过玻璃化冷冻心脏来研究热机械应力,同时探索纳米升温辅助从低温储存中恢复的效果。本研究扩展了最近发表的一项研究,将低温保存的实验研究与热分析相结合,使用大鼠心脏模型。具体来说,本研究侧重于具有可变浓度的硅涂层氧化铁纳米粒子(sIONP)的情况,同时考虑到与心脏生理学相关的负载限制,以及冷冻保护剂(CPA)溶液的性质和容器的几何形状。本研究的结果表明,与数学简化的均匀分布情况相比,基于心脏生理学的可变 sIONP 浓度会增加机械应力。在从低温储存中恢复器官的过程中,玻璃化转变以下和纳米升温超过玻璃化转变温度开始的最危险的再升温阶段。在整个再升温过程中,再升温较快的区域,如心脏腔室(较高的 sIONP 浓度),会经历压缩应力,而再升温较慢的区域,如心脏心肌(较低的 sIONP 浓度),则会经历张力。作为一种脆性材料,预计在较低的应力下,玻璃化的器官会在张力下失效,而不是在压缩下失效。不幸的是,在所研究的案例中,最大应力的位置和大小都有所不同,而没有确定一般规则。本研究表明,需要根据具体情况定制心脏冷冻保存的热方案,因为无法事先预测最大机械应力的位置、方向、大小和出现时刻。尽管热机械应力对器官完整性构成重大风险,但仔细设计热方案可以在充分利用纳米升温优势的同时,减少结构损坏的可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5236/10431620/a1f43b17950d/pone.0290063.g001.jpg

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