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Thermal Expansion of Cryoprotective Agents Combined with Synthetic Ice Blockers

冷冻保护剂与合成冰阻断剂结合的热膨胀

基本信息

批准号：
8100247
负责人：
YOED RABIN
金额：
$ 22.81万
依托单位：
CARNEGIE-MELLON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-09-01 至 2013-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8100247
关键词：
Accounting Address Affect Automobile Driving Behavior Biocompatible Materials Biological Biological Preservation Biology Biomedical Engineering Blood Vessels Cardiovascular system Cells Complex Computer Simulation Contracts Cornea Coupled Cryopreservation Cryoprotective Agents Crystal Formation Crystallization Data Development Devices Discipline Engineering Foundations Fracture Freezing Future Glass Growth Heart Valves Heating Histocompatibility Testing Ice Injury Investigation Knowledge Left Liquid substance Literature Measurement Measures Mechanical Stress Mechanics Medicine Mission Modeling Motivation Names Nature Operative Surgical Procedures Organ Outcome Pathology Play Process Property Protocols documentation Recovery Recovery of Function Regenerative Medicine Relaxation Research Research Proposals Research Technics Rewards Risk Role Science Shapes Solid Solutions Specimen Staging Stem cells Structure Study Section System Techniques Technology Temperature Terminology Time Tissue Banking Tissue Banks Tissue Engineering Tissue Model Tissues Toxic effect Work cost cryobiology cryogenics design high reward high risk improved physical property prevent programs public health relevance research study response soft tissue success tool transplantation medicine

项目摘要

DESCRIPTION (provided by applicant): The role of cryopreservation for tissue banking is undisputable, being the only practical alternative for long-term storage of high quality biomaterial. Successful techniques for cryopreservation have been developed for many cellular systems, but extrapolation to organized tissues and organs is fraught with additional problems that have only recently begun to be addressed. This, coupled with the growing need for cryobanking as an enabling technology for tissue engineering and regenerative medicine, has generated a priority need for a greater control of the additional mechanisms of injury responsible for the poor recovery of large-scale specimens after cryopreservation. The principal challenges revolve around avoiding tissue damage from ice formation (the cornerstone of cryoinjury) and from the thermo-mechanical stress generated during cooling and warming, with fracture formation as its most dramatic outcome. With recent promising results, the application of cryopreservation by means of vitrification (vitreous in Latin means glassy), where ice crystallization is suppressed, has become widely recognized as the only alternative for large-scale cryopreservation. However, cryopreservation by means of vitrification has its own difficulties, essentially resulting from toxicity effects associated with the high concentration of cryoprotective agents (CPAs) needed, and from the high thermo-mechanical stresses generated due to the high cooling rates required to promote vitrification. With the recent application of the so-called synthetic ice blockers (SIBs), successful large-scale cryopreservation via vitrification appears closer than ever before, where the concentration of the CPA can be significantly reduced, and the critical cooling rate to achieve vitrification is significantly lowered. However, the effect of the added SIBs on the developing thermo-mechanical stress is yet unknown, where the solid mechanics properties of the CPA+SIB cocktail are unexplored. Exploring the effects of SIBs on thermal expansion of the cryopreservation cocktail is the subject matter of the current research proposal, where thermal expansion is the driving mechanism of thermo-mechanical stress. Specifically, the objective in this study is to measure (for the first time) the thermal expansion coefficients of selected promising CPA+SIB cocktails, and compare the results with previously established data on the same CPAs in the absence of SIBs. In addition, results will be integrated into computer simulations of selected vitrification processes, to identify the significance of the measured property values. Consistent with the exploratory nature of this R21 research proposal, results of this study will serve as the foundation for a future research program on the application of SIBs in large-scale cryopreservation, and their effects on the structural integrity of the specimen. PUBLIC HEALTH RELEVANCE: Cryopreservation is the only practical alternative for long-term storage of high quality biomaterial for the benefit of transplantation medicine. The objective of the current proposal is to explore the thermal expansion of recently discovered cryoprotective solutions, where thermal expansion is the driving mechanism of fracture formation in large-scale cryopreservation. The measured data will be integrated into computer simulations and will be used to predict the likelihood of fracture formation in specific cryopreservation protocols.

描述（由申请人提供）：冷冻保存在组织库中的作用是无可争议的，是长期储存高质量生物材料的唯一实际选择。成功的冷冻保存技术已经发展到许多细胞系统，但外推到有组织的组织和器官充满了额外的问题，直到最近才开始解决。这一点，再加上对冷冻银行作为组织工程和再生医学的支持技术的日益增长的需求，已经产生了一个优先需要更好地控制造成大规模冷冻保存后标本恢复不良的额外损伤机制。主要的挑战是如何避免结冰造成的组织损伤（低温损伤的基础），以及在降温和升温过程中产生的热机械应力造成的组织损伤，裂缝形成是其最显著的结果。近年来，玻璃化（玻璃体）冷冻保存技术的应用取得了可喜的成果