Nanowarming-enabled vitrification for banking human livers

Abstract Summary Liver disease claims overlives every year in the U SaloneUnfortunatelythere are no dialysis or left ventricular assist device equivalents for liver failure and a liver transplant is the only treatmentYet thousands of potentially transplantable livers are discarded every year due to limitations in organ preservation timeswhich are on the order of hoursThe broad objective of this program is the development of a comprehensive system for the long term banking of livers for transplantationThis system will dramatically extend preservation times for human liversthus increasing the availability and efficient use of transplantable donor liversOur approach combines the best strategies for cryopreserving tissues in a vitreousglassyoramorphousstate with a novelbreakthrough nanowarming technologywhich utilizes infused radiofrequency excited biocompatible nanoparticles to rewarm tissueUnique to this technologynanowarming can rewarm large tissue volumes rapidly and uniformlywhich mitigates one of the major challenges in scaling cryopreservation technology to whole organsice growth and fracturing cracking of tissues during the critical rewarming phasesIn this projectwe will integrate recent advances in machine perfusion with optimized loading unloading proceduresnext generation non toxic cryopreservation solutionsinnovative breakthrough nanowarming technologies using biocompatible nanoparticlesand powerful tissue imaging methodse gcryomacroscopyuCTMRIto enable a convergence of state of the art technologies to develop a comprehensive preservation protocol that will maximize tissue viabilityIn Aimsandwe use representative precision cut liver slicesup tomls volumeto select the best available vitrification cocktail specific for liver tissue and to determine the critical cooling and critical warming rates required to achieve ice free and stress free cooling and warmingIn Aima comprehensive multi thermic machine perfusionMTMPprotocol will be applied to the whole rat liver to validate tolerance to the addition and removal of the vitrification cocktailfrom Aimcontaining nanoparticlesFinallywhole rat livers will be vitrified using the comprehensive MTMP protocol determined in Aimsand rewarmed via nanowarming to show feasibility for successful vitrification and nanowarming without damaging ice crystal formation or tissue fracturingVitrified whole livers rewarmed using traditional convective methods will serve as a control group for comparisonAltogetherthis constitutes an important standalone project whose substrategies are generally applicable and scalable to improve the long term preservation of cellstissuesand whole organsThe subsequent Phase II study will target optimization of the MTMP nanowarming protocol for the preservation of transplant quality liver function and scale up to human liversImportantlysuccess of these novel sub strategiesMTMPnanowarmingetcindividually or in combination will likely enable further breakthroughs in biopreservationtissue engineeringbioemedical research and clinical practice Narrative Liver transplantation is the only treatment for the tens of thousands of patients suffering from liver failure in the U Syet thousands of potentially transplantable livers are discarded each yearThe ability to preserve donor liversand organs in generalcould be life saving for hundreds of thousandsif not millionsof people around the worldIn recent decadescryopreservation technologies have allowed for damage freeindefinite storage of tissuesbut similar advances to prevent damaging ice growthand or fracturing during tissue rewarming are still neededTo overcome these barrierswe have developed a novel strategy combining organ perfusion and nanowarming for long term liver preservationwhich has the potential to immediately make accessible lifepreserving liver transplants for emergency caseswhile facilitating widespread banking of all types of organs and tissues in the future