RF excited magnetic nanoparticles to improve thawing of vitrified biomaterials

CBET-1336659玻璃化或冷冻至a？glassy？而不是结晶相，是生物保存的一种形式，也是细胞和再生医学的一种重要方法。 原则上，这种方法提供了存储和运输细胞、组织和器官的强大能力，可用于生物医学实验室、生物银行组织和全球公司。 不幸的是，由于扩散（热量和质量传递）和相变限制，玻璃化的实际应用局限于较小的系统，例如细胞和薄组织。具体而言，解冻过程中的失透（结晶）和破裂排除了在散装系统（如器官和较大组织）中使用玻璃化。为了规避这一根本问题，我们在这里提出使用射频（RF）激发的磁性纳米颗粒（mNP），以创建均匀的热生成生物材料，从而避免大小或边界条件的依赖，可能会导致失败，在解冻过程中。 作为这项工作的一部分，我们将表征的加热和相变行为的mNP负载的冷冻保护解决方案。这将包括冷冻保护剂（CPA）和mNP（磁性纳米颗粒）的选择，这些解决方案的物理化学表征（即热和磁性，聚集和失透），以及RF解冻测量和建模，以证明优于传统方法的改进。在对mNP CPA溶液进行表征后，我们将研究更均匀和快速解冻对生物学结果的影响。在此，溶液将通过扩散或灌注加载到细胞和组织中，然后这些加载的系统将通过成像、染色和其他分析方法进行评估，以证明CPA和mNP加载的位置。此外，将确定在冷却期间玻璃化并避免解冻时失透或开裂所需的临界冷却和升温速率。最后，改善这些系统的生存能力和结构，避免失透和开裂后，RF激发mNP解冻将demonstration.This项目有可能显着提高生物材料的玻璃化，因此生物保存影响细胞库和治疗，组织移植和其他重要的再生医学和生物医学应用世界各地。 我们的方法将产生更快，更均匀的解冻速率，预计将提高生物保护系统解冻后的生存力和结构完整性。这项新技术最引人注目的机会将用于较大的生物材料，其中失透和开裂通常会导致保存失败，并且更快的解冻速率也可能有助于减少所需的潜在有毒CPA的量。更广泛地说，拟议的研究将使人们更好地了解冷冻和玻璃化生物系统中纳米颗粒的相互作用，其潜在应用超出了生物保存的范围。 所进行的研究将为几个研究生和本科生提供教育机会，并与学术界和工业界的同事合作。

CBET-1336659BischofVitrification or freezing to a ?glassy? rather than crystalline phase, is a form of biopreservation and an important enabling approach for cellular and regenerative medicine. In principle, this approach offers the powerful ability to store and transport cells, tissues and organs which can be used in biomedical labs, biological banking organizations and companies worldwide. Unfortunately, practical application of vitrification has been limited to smaller systems such as cells and thin tissues due to diffusive (heat and mass transfer) and phase change limitations. Specifically, devitrification (crystallization) and cracking during thawing preclude the use of vitrification in bulk systems such as organs and larger tissues. To circumvent this fundamental problem we propose here to use radiofrequency (RF) excited magnetic nanoparticles (mNPs) to create uniform heat generation within biomaterials thereby avoiding size or boundary condition dependence which can lead to failure during thawing. As a part of this work, we will characterize the heating and phase change behavior of mNP-laden cryoprotective solutions. This will include selection of cryoprotective agent (CPA) and mNPs (magnetic nanoparticles), physicochemical characterization of these solutions (i.e. thermal and magnetic properties, aggregation, and devitrification), and RF thawing measurement and modeling to demonstrate improvements over traditional approaches. After characterizing the mNP CPA solutions we will investigate the impact of more uniform and rapid thaw on biological outcomes. Here the solutions will be loaded into cells and tissues by diffusion or perfusion, then these loaded systems will be assessed by imaging, staining and other analytical approaches to demonstrate where the CPA and mNPs have loaded. Further, the critical cooling and warming rates necessary to vitrify during cooling and avoid devitrification or cracking upon thaw will be determined. Finally, improvements to the viability and structure of these systems by avoiding devitrification and cracking after RF excited mNP thawing will be demonstrated.This project has the potential to dramatically improve biomaterial vitrification and therefore biopreservation which impacts cell banking and therapies, tissue transplantation and other important regenerative medicine and biomedical applications worldwide. Our approach will yield faster and more uniform thawing rates that are expected to improve both viability and structural integrity upon thawing of biopreserved systems. The most dramatic opportunity of this new technology will be use for larger biomaterials where devitrification and cracking routinely result in preservation failures, and where faster thaw rates may also help reduce the amount of potentially toxic CPAs needed. More broadly, the proposed research will lead to greater understanding of the interactions of NPs within frozen and vitrified biological systems, with potential applications that go beyond biopreservation. The research undertaken will provide educational opportunities for several graduate and undergraduate students and collaboration with both academic and industrial colleagues.