Department of Mechanical Engineering, University of Minnesota, Minneapolis, MN, 55455, USA.
Department of Surgery, University of Minnesota, Minneapolis, MN, 55455, USA.
Adv Sci (Weinh). 2021 Oct;8(19):e2101691. doi: 10.1002/advs.202101691. Epub 2021 Aug 11.
Vitrification can dramatically increase the storage of viable biomaterials in the cryogenic state for years. Unfortunately, vitrified systems ≥3 mL like large tissues and organs, cannot currently be rewarmed sufficiently rapidly or uniformly by convective approaches to avoid ice crystallization or cracking failures. A new volumetric rewarming technology entitled "nanowarming" addresses this problem by using radiofrequency excited iron oxide nanoparticles to rewarm vitrified systems rapidly and uniformly. Here, for the first time, successful recovery of a rat kidney from the vitrified state using nanowarming, is shown. First, kidneys are perfused via the renal artery with a cryoprotective cocktail (CPA) and silica-coated iron oxide nanoparticles (sIONPs). After cooling at -40 °C min in a controlled rate freezer, microcomputed tomography (µCT) imaging is used to verify the distribution of the sIONPs and the vitrified state of the kidneys. By applying a radiofrequency field to excite the distributed sIONPs, the vitrified kidneys are nanowarmed at a mean rate of 63.7 °C min . Experiments and modeling show the avoidance of both ice crystallization and cracking during these processes. Histology and confocal imaging show that nanowarmed kidneys are dramatically better than convective rewarming controls. This work suggests that kidney nanowarming holds tremendous promise for transplantation.
玻璃化可以显著提高在低温状态下储存生物材料的存活时间,可达数年。不幸的是,目前像大型组织和器官等体积≥3ml 的玻璃化系统,不能通过对流方法足够迅速或均匀地再加热,以避免冰晶形成或破裂失效。一种新的体积再加热技术,称为“纳米加热”,通过使用射频激发的氧化铁纳米颗粒来快速均匀地再加热玻璃化系统,解决了这个问题。在这里,首次展示了使用纳米加热成功地从玻璃化状态下恢复大鼠肾脏。首先,通过肾动脉将冷冻保护剂鸡尾酒(CPA)和涂有二氧化硅的氧化铁纳米颗粒(sIONPs)灌注到肾脏中。在控速冷冻机中以-40°C/min 的冷却速度冷却后,使用微计算机断层扫描(µCT)成像来验证 sIONPs 的分布和肾脏的玻璃化状态。通过施加射频场来激发分布的 sIONPs,玻璃化的肾脏以 63.7°C/min 的平均速率进行纳米加热。实验和模拟表明,在这些过程中既避免了冰晶形成,也避免了破裂。组织学和共聚焦成像显示,纳米加热的肾脏明显优于对流再加热对照。这项工作表明,肾脏纳米加热在移植方面具有巨大的潜力。