Improved Tissue Cryopreservation Using Inductive Heating of Magnetic Nanoparticles

Vitrification, a kinetic process of liquid solidification into glass,poses many potential benefits for tissue cryopreservation includingindefinite storage, banking, and facilitation of tissuematching for transplantation. To date, however, successful rewarmingof tissues vitrified in VS۵۵, a cryoprotectant solution,can only be achieved by convective warming of small volumeson the order of ۱ ml. Successful rewarming requires both uniformand fast rates to reduce thermal mechanical stress andcracks, and to prevent rewarming phase crystallization. We presenta scalable nanowarming technology for ۱- to ۸۰-ml samplesusing radiofrequency-excited mesoporous silica-coatediron oxide nanoparticles in VS۵۵. Advanced imaging includingsweep imaging with Fourier transform and microcomputed tomographywas used to verify loading and unloading of VS۵۵and nanoparticles and successful vitrification of porcine arteries.Nanowarming was then used to demonstrate uniform andrapid rewarming at>۱۳۰°C/min in both physical (۱ to ۸۰ ml)and biological systems including human dermal fibroblast cells,porcine arteries and porcine aortic heart valve leaflet tissues (۱to ۵۰ ml). Nanowarming yielded viability that matched controland/or exceeded gold standard convective warming in ۱- to ۵۰-ml systems, and improved viability compared to slow-warmed(crystallized) samples. Last, biomechanical testing displayedno significant biomechanical property changes in blood vessellength or elastic modulus after nanowarming compared tountreated fresh control porcine arteries. In aggregate, theseresults demonstrate new physical and biological evidence thatNanowarming can improve the outcome of vitrified cryogenicstorage of tissues in larger sample volumes.