Cryopreservation mechanisms in blood vessels using ice modulators

 描述：低温保存对组织银行和移植医学的重要性是毋庸置疑的，是长期保存高质量生物材料的唯一实用选择。虽然在过去50年中发展了成功的冷冻保存技术，但它们通常与小标本有关，从细胞团的规模范围到小组织(微米到毫米范围)，以干细胞和角膜为例。以心脏瓣膜为例，只有在机械功能的需要高于生物功能恢复的情况下，才能完成较大尺寸的标本(厘米及以上)的超低温保存。然而，近年来，冷冻保存的科学技术有了长足的进步，冷冻保存在大型组织结构和器官中的成功应用比以往任何时候都更加紧密。冷冻保存的成功主要围绕着控制冰的形成--这是冷冻损伤的基石。目前的研究重点是通过存在被称为低温保护剂(CPA)的高粘度材料来抑制结晶，这一过程被称为验证(Vitreous在拉丁语中的意思是玻璃)。虽然玻璃化是一种众所周知的现象，但它在生物系统中的应用伴随着CPA的毒性和由于热机械应力造成的结构破坏的潜在有害影响。事实上，这些影响代表着对选择CPA及其浓度非常重要的竞争需求，并对低温保存技术的发展构成了重大障碍。目前的项目试图通过将合成冰调制器(SIMS)与影响冰晶形成和生长的CPA鸡尾酒相结合来缓解这种耦合。该项目代表了一种研究冷冻保存的整体方法。研究团队汇集了生物、化学、物理、热工和固体力学等不同领域的专业知识，同时将建模工具与实验研究相结合。最近已经提出了大量关于用选定的SIMs进行玻璃化冷冻保存的数据，因为它们与小血管段和环有关。目前的项目目标是扩大血管冷冻保存的规模，将其作为冷冻保存应用于大型组织、器官和工程化组织结构的关键构建块。相关技术是可翻译的，应用的科学和工程工具本质上是相同的，这意味着本研究的潜在影响。该项目的具体目标是：(I)测量生物材料的关键物理性质，(Ii)对相关物理事件，如结晶和破裂进行冷冻宏观调查，(Iii)调查材料的机械行为，(Iv)评估冷冻保存后标本的活性和功能恢复，以及(V)结合在其他特定目标中发展的知识，通过玻璃化冷冻来模拟冷冻保存。这种建模被认为是未来技术开发和流程优化的重要工具。

 DESCRIPTION: The importance of cryopreservation for tissue banking and transplant medicine is indisputable, being the only practical alternative for long-term storage of high quality biomaterials. While successful techniques for cryopreservation have been developed over the past five decades, they are generally related to small specimens, in the scale-range of cell clusters to small-organized tissues (µm to mm range), with stem cells and corneas as examples. Cryopreservation of larger-size specimens (cm and above) has been accomplished only in cases where the mechanical functionality has a higher priority need than the recovery of biological functionality, with heart valves as an example. Nevertheless, the science and technology of cryopreservation have dramatically advanced in recent years, and the successful application of cryopreservation to large tissue structures and organs is closer than ever before. Cryopreservation success revolves essentially around controlling ice formation-the cornerstone of cryoinjury. The current research focuses on suppressing crystallization by the presence of highly viscous materials, known as cryoprotective agents (CPAs), in a process known as verification (vitreous in Latin means glassy). While vitrification is a well-understood phenomenon, its application to biological systems comes with the potentially harmful effects of toxicity of the CPA and structural damage due to thermo-mechanical stresses. In fact, these effects represent competing needs important for selecting CPAs and their concentrations, and represent a significant barrier to the development of cryopreservation technology. The current project seeks to alleviate this coupling by combining synthetic ice-modulators (SIMs) with the CPA cocktail, which influence the formation and growth of ice crystals. This project represents a holistic approach to the study of cryopreservation. The research team brings together expertise from the disparate fields of biology, chemistry, physics, thermal engineering, and solid mechanics, while combining modeling tools with experimental investigation. Substantial data has been presented recently on cryopreservation by vitrification with a selected set of SIMs, as they pertain to small blood vessel segments and rings. The current project targets scale-up cryopreservation of blood vessels as key building blocks for cryopreservation applications in bulky tissues, organs, and engineered tissue constructs. The relating technology is translational and the applied scientific and engineering tools are essentially the same, which signifies the potential impact of this study. Specific aims for this project are: (i) to measure key physical properties of the biomaterials, (ii) to perform cryomacroscopic investigation of relevant physical events such as crystallization and fracturing, (iii) to investigate the mechanical behavior of the materials, (iv) to evaluate viability and functional recovery of the specimen post cryopreservation, and (v) to model cryopreservation by vitrification while integrating the knowledge developed in the other specific aims. This modeling is deemed an essential tool for future technology developments and process optimization.