MOLECULAR ICE CONTROL FOR ENGINEERED TISSUES

描述(由申请人提供)：长期保存是至关重要的 组织工程的使能技术。冷冻保存将提供一种 这一需求的理想解决方案，除了复合体中的冰结晶 多组分组织对细胞和细胞外基质造成损伤 使组织失去功能。玻璃体冷冻保存可稳定玻璃体 作为玻璃的生物系统，从而避免了冰结晶，导致 显著改善了超低温保存。然而，玻璃化并非易事。 在与临床应用相关的批量样本中实现，因为 对达到足够高的冷却和升温速率的限制 防止结冰。银行业务的终极目标自然而精心设计 使用玻璃化冷冻的组织只有在适当的方法下才能实现 控制冰层增长的方法。这项研究的重点是一种新的方法 结合常规冷冻保护控制复杂组织中的冰 含有合成阻冰剂(SIB)分子和自然生成的试剂 抗冻肽。SIB是一系列专利分子，设计于 限制冰成核和生长的分子模拟研究的基础。 现有的和新设计的SIB将应用于设计的挑战 玻璃化大块样品的解决方案，而不会损坏冰块和展示 血管移植物长期保存的可行性。 建议的商业应用： 本申请中提出的技术开发将使新兴的组织工程行业能够更有效和高效地利用组织保存方面的新发展。目前的组织和细胞储存方法存在着公认的与结冰相关的技术问题。器官回收系统公司(ORS)的主要目标是开发用于储存和运输生物材料、组织和器官的方法和设备，用于体外和体内使用。最终，同种异体移植和组织工程的成功都取决于实用的产品储存和运输方法的可用性。目前用于无限制储存和稳定细胞和组织的唯一方法涉及到低温生物学的应用。潜在的市场是巨大的。低温保存方法将被许可给组织工程行业，这种方法可以保留活性和功能。

DESCRIPTION (provided by applicant): Long term preservation is crucial as an enabling technology for tissue engineering. Cryopreservation would provide an ideal solution to this need except that ice crystallization in complex multicomponent tissues causes injury to the cells and the extracellular matrix rendering the tissue nonfunctional. Vitreous cryopreservation that stabilizes the biosystem as a glass, thereby avoiding ice crystallization, leads to markedly improved cryopreservation. However, vitrification is not easily achieved in bulk samples relevant to clinical applications because of constraints on attaining sufficiently high cooling and warming rates to preclude ice formation. The ultimate goal of banking natural and engineered tissues using vitrification will be achieved only if adequate methods of controlling ice growth are devised. This study is focused on a novel approach to controlling ice in complex tissues by combining conventional cryoprotective agents with synthetic ice blocker (SIB) molecules and naturally-occurring antifreeze peptides. SIBs are a series of proprietary molecules designed on the basis of molecular-modeling studies to limit ice nucleation and growth. Existing and newly designed SIBs will be applied to the challenge of designing solutions for vitrifying bulk samples without ice damage and showing feasibility for the long-term storage of vascular grafts. PROPOSED COMMERCIAL APPLICATIONS: The technology development proposed in this application will enable the emerging tissue engineering industry to make more effective and efficient use of new developments in tissue preservation. Current tissue and cell storage methods have well-recognized technical problems associated with ice formation. A primary goal of Organ Recovery Systems, Inc. (ORS) is development of methods and devices for storage and transportation of biological materials, tissues and organs for both in vitro and in vivo use. Ultimately, the success of both allogeneic transplantation and tissue engineering depends upon the availability of practical product storage and transportation methods. The only methods currently used for unlimited storage and stabilization of cells and tissues involve the application of cryobiology. The potential markets are enormous. Cryopreservation methods, which result in retained viability and function, will be licensed to the tissue engineering industry.