Cryopreservation mechanisms in blood vessels using ice modulators

使用冰调制器的血管冷冻保存机制

• 批准号: 9274845
• 负责人: YOED RABIN
• 金额: $ 39.63万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-04 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9274845
• 关键词: Biocompatible Materials; Biological Preservation; Biological Process; Biology; Blood Vessels; Cells; Chemistry; Communities; Complex; Computer Simulation; Cornea; Coupled; Coupling; Cryopreservation; Cryoprotective Agents; Crystallization; Data; Databases; Development; Device or Instrument Development; Devices; Elasticity; Engineering; Evaluation; Event; Exposure to; Fracture; Future; Glass; Goals; Growth; Heart Valves; Ice; Imagery; Investigation; Kinetics; Knowledge; Measures; Mechanical Stress; Mechanics; Medicine; Methods; Mind; Modeling; Organ; Physics; Process; Protocols documentation; Recovery; Recovery of Function; Relaxation; Research; Research Personnel; Research Proposals; Rewarming; Risk; Sampling; Science; Site; Solid; Specimen; Stem cells; Stress; Structure; System; Techniques; Technology; Testing; Thermal Conductivity; Tissue Engineering; Tissue Preservation; Tissues; Toxic effect; Universities; Viscosity; Work; base; biological systems; cold temperature; cryobiology; cryogenics; design; enthalpy; holistic approach; improved; innovation; mechanical behavior; member; multidisciplinary; physical property; polarized light; prevent; process optimization; programs; public health relevance; scale up; success; technology development; tissue/organ preservation; tool; transplantation medicine

 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.

 描述：冷冻保存对于组织库和移植医学的重要性是无可争议的，它是长期储存高质量生物材料的唯一实用替代方案。尽管在过去的五年中已经开发出了成功的冷冻保存技术，但它们通常与小型技术有关。样本，从细胞簇到小组织组织（微米到毫米范围）的尺度范围，以干细胞和角膜为例。仅在机械功能比恢复生物功能具有更高优先级的情况下才能实现功能，以心脏瓣膜为例，尽管如此，近年来冷冻保存的科学技术已经取得了巨大的进步，并且得到了成功的应用。冷冻保存对大型组织结构和器官的影响比以往任何时候都更接近冷冻保存的成功主要围绕控制冰的形成——冷冻损伤的基石当前的研究重点是通过高粘性材料的存在来抑制结晶。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会带来 CPA 毒性和结构损伤的潜在有害影响。事实上，这些效应代表了选择 CPA 及其浓度的重要竞争需求，并且是冷冻保存技术发展的重大障碍。当前的项目旨在通过结合合成来缓解这种耦合。该项目代表了冷冻保存研究的整体方法，该研究团队汇集了生物学、化学、物理学等不同领域的专业知识。热工程和固体力学，同时将建模工具与实验研究相结合，最近提出了使用一组选定的 SIM 进行玻璃化冷冻保存的大量数据，因为它们与小血管段和环有关。该项目的目标是扩大血管冷冻保存的规模，作为大体积组织、器官和工程组织构建体冷冻保存应用的关键组成部分。相关技术是可转化的，所应用的科学和工程工具本质上是相同的，这表明了该技术的潜在影响。该研究的具体目标是：（i）测量生物材料的关键物理特性，（ii）对结晶和断裂等相关物理事件进行低温宏观研究，（iii）研究机械性能。材料的行为，（iv）评估冷冻保存后样本的可行性和功能恢复，以及（v）通过玻璃化对冷冻保存进行建模，同时整合在其他特定目标中开发的知识。该建模被认为是未来技术的重要工具。发展和流程优化。