Thermo mechanical stress in cryopreserved blood vessels

描述（由申请人提供）：低温保存技术代表了一种潜在的长期和最小损害的方法来保存原生和工程组织。同种异体静脉的常规冷冻保存目前正在临床应用，但在动物模型和患者中使用这些移植物的体内研究表明，长期通畅率很低。另一种冷冻保存方法是玻璃化，避免了冰形成的危害，从而在结构和功能方面显著改善了血管产物。玻璃化（vitreous在拉丁语中意为玻璃状）本质上是通过调整化学成分和冷却速度使过冷液体凝固，从而避免晶体相。这种新的保存技术现在正在扩大应用于临床标本和最终工程血管。然而，为了成功地低温保存组织，必须避免与大块玻璃化标本中的热机械应力相关的额外危险。我们的长期目标是减少在组织低温保存过程中引起的破坏性机械应力，特别是血管。本研究的目的是开发工程工具，表征大块低温保存组织中的热机械应力水平，从而设计技术来减少或规避这些应力，并开发改进的天然和工程血管移植物长期储存的方法。具体目的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-机械应力进行系统的研究。通过适当的数学建模和计算机模拟，测量参数将为最小化热机械应力和减少低温保存过程中裂缝形成的可能性提供指导。虽然本研究的实验工作是针对血管的，但本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物。

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.