Oscillating Magnetic Field Assisted Supercooling Preservation of Fresh and Unfrozen Ovaries at Subzero Temperatures

振荡磁场辅助在零下温度下过冷保存新鲜和未冷冻的卵巢

• 批准号: 10821622
• 负责人: Soojin Jun
• 金额: $ 27.5万
• 依托单位: JUN INNOVATIONS, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-25 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10821622
• 关键词: 3-Dimensional; Affect; Assisted Reproductive Technology; Automobile Driving; Biocompatible Materials; Biological; Biological Preservation; Butylene Glycols; Cancer Patient; Cardiac Myocytes; Cells; Cellular Structures; Characteristics; Chemicals; Chills; Clinical; Complex; Computer software; Control Groups; Cryopreservation; Cryoprotective Agents; Dehydration; Deterioration; Devices; Dimethyl Sulfoxide; Elements; Engineering; Ensure; Equilibrium; Fertility; Foundations; Freezing; Gene Expression; Goals; Growth; Human; Ice; Injury; Legal patent; Life; Liquid substance; Membrane; Metabolic; Methods; Mus; Neuronal Differentiation; Oocytes; Organ; Organ Preservation; Osmosis; Outcome; Ovarian; Ovarian Tissue; Ovary; Phase; Preservation Technique; Process; Property; Protocols documentation; RNA; Radiation therapy; Recipe; Recovery; Sampling; Solid; Stress; Structure; System; Techniques; Technology; Temperature; Testing; Time; Tissue Preservation; Tissues; Toxic effect; Transplantation; Transportation; Water; biological systems; chemotherapy; cold temperature; commercialization; cytotoxicity; design; extracellular; fertility preservation; granulocyte; hazard; innovation; insight; invention; magnetic field; matrigel; melting; natural hypothermia; novel; organizational structure; phase 1 study; phase change; preservation; tissue culture; transcriptome sequencing

PROJECT SUMMARY/ABSTRACT When the internal temperature of a material during freezing is below its equilibrium freezing point before ice nucleation has occurred, the material is said to be in the supercooled state. The long-term objective of this project is to develop a novel commercially viable supercooling device to preserve biological materials far below their freezing points while retaining their functionalities live. Engineered magnetic fields in the oscillation mode has been proved to control the discharge and realignment of water molecules using diamagnetic properties of water molecules. Therefore, water in biological materials can remain unfrozen at subzero temperatures when magnetic fields are applied. Among many other materials for cryopreservation and organ banking, we have selected the whole mice ovary for our focused proof of concept. The developed supercooling technology will enable an extended storage duration as well as higher recovery rates of ovarian functionalities with zero toxicity, compared to classic cryopreservation methods. In the Phase I study, the supercooling technology will be tested for an extended supercooling status of mice ovaries at -5 to -10 °C for up to 4 weeks, and their preserved fertilities will be examined. We anticipate a robust and stabilized solution for hypothermic yet non-freezing preservation of diverse biological samples, i.e. cells, tissues, and organs, by extension. In the past several years, a number of studies have appeared questioning the functional qualities of biological materials stored using conventional cryopreservation methods. They indicated that (i) biological systems have highly organized structures that are extremely sensitive to freezing/thawing processes and (ii) high concentrations of cryoprotective agents (CPAs) such as dimethyl sulfoxide (DMSO) are potentially toxic. When the biological sample is cooled below its melting point, or equilibrium freezing temperature, water within the cellular structure will undergo a phase change from liquid to solid. The formation of extracellular ice is known to be a hazard to structured tissues and organs. In addition, DMSO shows high cytotoxicity and affects the differentiation of neuron-like cells, cardiac myocytes, and granulocytes, and needs to be eliminated rapidly after thawing. The developed technique will offer the technical feasibility and solid foundations for any full-organ or complex tissue preservation efforts, providing insight into potential structural and functional effects of the preservation process on high-content, complex and human-derived organs.

项目概要/摘要 当冻结期间材料的内部温度低于其平衡冻结时 在冰成核发生之前的点，材料被认为处于过冷状态。这 该项目的长期目标是开发一种新型的商业上可行的过冷装置 将生物材料保存在远低于其冰点的同时保留其 功能已上线。振荡模式下的工程磁场已被证明 利用水的抗磁特性控制水分子的排放和重新排列 分子。因此，生物材料中的水可以在零下温度下保持不冻结 当施加磁场时。用于冷冻保存和器官的许多其他材料 银行业务，我们选择了整个小鼠卵巢作为我们重点的概念验证。这 开发的过冷技术将能够延长存储时间以及更高的 与传统冷冻保存相比，卵巢功能恢复率为零毒性 方法。在第一阶段研究中， 过冷技术将进行长期测试 小鼠卵巢在-5至-10的过冷状态 °C 长达 4 周，并保存 将检查生育能力。我们期望为低温尚未解决的稳健和稳定的解决方案 非冷冻保存多种生物样品，即细胞、组织和器官， 扩大。在过去的几年里，许多研究对功能性的问题提出了质疑。 使用传统冷冻保存方法储存的生物材料的质量。他们 表明（i）生物系统具有高度组织化的结构，并且极其敏感 冷冻/解冻过程和 (ii) 高浓度冷冻保护剂 (CPA)，例如 因为二甲基亚砜 (DMSO) 具有潜在毒性。当生物样品冷却至以下时 其熔点或平衡冰点温度，细胞结构内的水将 经历从液态到固态的相变。众所周知，细胞外冰的形成是 对结构组织和器官的危害。此外，DMSO 显示出高细胞毒性并影响 神经元样细胞、心肌细胞和粒细胞的分化，需要 解冻后迅速消除。所开发的技术将提供技术可行性和 为任何全器官或复杂组织保存工作奠定坚实的基础，提供深入了解 保存过程对高含量、复杂物质的潜在结构和功能影响 和人体器官。