Research ArticleNanotechnology

Improved tissue cryopreservation using inductive heating of magnetic nanoparticles

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Science Translational Medicine  01 Mar 2017:
Vol. 9, Issue 379, eaah4586
DOI: 10.1126/scitranslmed.aah4586

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Improved tissue cryopreservation with nanowarming

Organ transplantation is limited by the availability of viable donor organs. Although storage at very low temperatures (cryopreservation) could extend the time between organ harvest and transplant, the current gold standard for rewarming (convection) leads to cracking and crystallization in samples larger than a few milliliters. Manuchehrabadi et al. demonstrate the rewarming of cells and tissues by radiofrequency inductive heating using magnetic nanoparticles suspended in a cryoprotectant solution. This nanowarming technique rapidly and uniformly rewarmed cryopreserved fibroblasts, porcine arteries, and porcine heart tissues in systems up to 50 ml in volume, yielding tissues with higher viability than convective rewarming.

Abstract

Vitrification, a kinetic process of liquid solidification into glass, poses many potential benefits for tissue cryopreservation including indefinite storage, banking, and facilitation of tissue matching for transplantation. To date, however, successful rewarming of tissues vitrified in VS55, a cryoprotectant solution, can only be achieved by convective warming of small volumes on the order of 1 ml. Successful rewarming requires both uniform and fast rates to reduce thermal mechanical stress and cracks, and to prevent rewarming phase crystallization. We present a scalable nanowarming technology for 1- to 80-ml samples using radiofrequency-excited mesoporous silica–coated iron oxide nanoparticles in VS55. Advanced imaging including sweep imaging with Fourier transform and microcomputed tomography was used to verify loading and unloading of VS55 and nanoparticles and successful vitrification of porcine arteries. Nanowarming was then used to demonstrate uniform and rapid rewarming at >130°C/min in both physical (1 to 80 ml) and biological systems including human dermal fibroblast cells, porcine arteries and porcine aortic heart valve leaflet tissues (1 to 50 ml). Nanowarming yielded viability that matched control and/or exceeded gold standard convective warming in 1- to 50-ml systems, and improved viability compared to slow-warmed (crystallized) samples. Last, biomechanical testing displayed no significant biomechanical property changes in blood vessel length or elastic modulus after nanowarming compared to untreated fresh control porcine arteries. In aggregate, these results demonstrate new physical and biological evidence that nanowarming can improve the outcome of vitrified cryogenic storage of tissues in larger sample volumes.

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