Thermo mechanical stress in cryopreserved blood vessels

描述（由申请人提供）：冷冻保存技术代表了一种潜在的长期和最小损伤的方法，用于保存天然和工程组织。涉及冷冻的同种异体静脉的常规冷冻保存目前正在临床上使用，但是在动物模型和患者中使用这些移植物的体内研究已经证明了较差的长期通畅率。另一种冷冻保存方法涉及玻璃化，避免了冰形成的危险，导致在结构和功能方面显着改善的血管产品。玻璃化（拉丁文中玻璃的意思是玻璃状的）本质上是通过调整化学成分和冷却速率使过冷液体凝固，从而避免结晶相。这种新的保存技术目前正在扩大应用于临床标本，并最终用于工程血管。然而，为了成功地冷冻保存组织，必须避免与批量玻璃化标本中的热机械应力相关的其他危害。我们的长期目标是减少一般组织，特别是血管冷冻保存过程中引起的破坏性机械应力。本研究的目的是开发工程工具，并表征大体积冷冻保存组织中的热机械应力水平，从而设计减少或规避这些应力的技术，并开发天然和工程血管移植物长期储存的改进方法。具体目标是通过测量热膨胀和应力-应变关系，对低温保存血管中的热机械应力进行系统研究。测量的参数与适当的数学建模和计算机模拟，将提供指导方针，以尽量减少热机械应力，并减少在低温保存过程中的裂缝形成的潜力。虽然这项研究中的实验工作是针对血管的，但这项研究的结果可以扩展并适用于各种冷冻保存的天然组织和工程构建体。

DESCRIPTION (provided by applicant): Cryopreservation technologies represent a potential long term and minimally damaging method to preserve both native and engineered tissues. Conventional cryopreservation of allogeneic veins involving freezing is currently being used clinically, but in vivo studies using these grafts in both animal models and patients have demonstrated poor long-term patency rates. An alternative approach to cryopreservation involving vitrification that avoids the hazards of ice formation leads to a markedly improved vascular product in terms of both structure and function. Vitrification (vitreous means glassy in Latin) is essentially the solidification of a supercooled liquid by adjusting the chemical composition and cooling rate such that the crystal phase is avoided. This new preservation technology is now being scaled up for application to clinical specimens and ultimately engineered blood vessels. Nevertheless, additional hazards related to thermo-mechanical stresses in bulk vitrified specimens must be avoided for successful cryopreservation of tissues. Our long term goal is to reduce the destructive mechanical stresses induced during cryopreservation of tissues in general, and of blood vessels in particular. The purpose of this research is to develop engineering tools and to characterize the level of thermo-mechanical stresses in bulky cryopreserved tissues and thereby devise techniques to reduce, or circumvent, these stresses and develop improved methods of long term storage of both native and engineered vascular grafts. The specific aims are to undertake a systematic study of thermo-mechanical stresses in cryopreserved blood vessels by measuring thermal expansion and stress-strain relationships. The measured parameters with appropriate mathematical modeling and computers simulations, will provide guidelines for minimizing the thermo-mechanical stresses and reduce the potential of fracture formation during cryopreservation. Although the experimental work in this study is targeted to blood vessels, the results of this study could be expanded and become useful for a wide variety of cryopreserved natural tissues and engineered constructs.