Cryopreservation mechanisms in blood vessels using ice modulators

 产品说明：冷冻保存对组织库和移植医学的重要性是无可争议的，是长期储存高质量生物材料的唯一可行的选择。虽然在过去的五十年中已经开发了成功的冷冻保存技术，但它们通常与小样本相关，在细胞簇到小组织组织的尺度范围内（μm到mm范围），以干细胞和角膜为例。仅在机械功能比生物功能恢复具有更高优先级需求的情况下，才完成较大尺寸标本（cm及以上）的冷冻保存，以心脏瓣膜为例。尽管如此，近年来冷冻保存的科学和技术已经取得了显着的进步，并且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接近。冷冻保存的成功基本上围绕着控制冰的形成-冷冻损伤的基石。目前的研究重点是在一个被称为验证（拉丁语中的玻璃质意味着玻璃状）的过程中，通过存在被称为低温保护剂（CPA）的高粘性材料来抑制结晶。虽然玻璃化是一种众所周知的现象，但其在生物系统中的应用伴随着CPA的毒性和由于热机械应力引起的结构损伤的潜在有害影响。事实上，这些影响代表了选择CPA及其浓度的重要竞争需求，并代表了冷冻保存技术发展的重大障碍。目前的项目旨在通过将合成冰调节剂（西姆斯）与CPA鸡尾酒相结合来减轻这种耦合，CPA鸡尾酒会影响冰晶的形成和生长。该项目代表了冷冻保存研究的整体方法。该研究团队汇集了来自生物学，化学，物理学，热工程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的数据，通过玻璃化冷冻保存与选定的一组西姆斯，因为它们属于小血管段和环。目前的项目目标是扩大血管的冷冻保存，作为冷冻保存在大体积组织，器官和工程组织结构中应用的关键构件。相关技术是转化的，应用的科学和工程工具基本上是相同的，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）进行相关物理事件（例如结晶和破裂）的低温宏观研究，（iii）研究材料的机械行为，（iv）评估冷冻保存后样本的存活力和功能恢复，以及（v）通过玻璃化模拟低温保存，同时整合在其他特定目标中开发的知识。这种建模被认为是未来技术发展和工艺优化的重要工具。

 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.