Optimal Rewarming Solutions for Cryopreserved Tissue Systems: Rapid rewarming reduction of cryoprotectant toxicity and concentration employing magnetic nanoparticles

Vitrification, cryopreserved storage in a “glassy” rather than crystalline phase, is an important enabling approach for tissue banking and regenerative medicine, offering the ability to store and transport cells, tissues and organs for a variety of biomedical uses without the risks of damaging ice formation. Unfortunately, practical application of vitrification has been limited to reproductive cells and thin tissues due to diffusive (heat and mass transfer) and phase change limitations that preclude use in bulk systems such as organs and larger tissues. In our Phase I SBIR we proposed use of radiofrequency excited magnetic nanoparticles, nanowarming, to aid in rewarming of tissues to circumvent this problem. We successfully demonstrated that nanowarming of vitrified heart valve segments is a feasible alternative to convection warming. Alternative formulations and protocols reducing risks of cryoprotectant-induced cytotoxicity were also developed. In Phase II we propose translation of this technology to vascularized composite allotransplants in a step wise manner using animal tissue models in vitro, followed by transplant studies and concluding with evaluation of nanowarming for ice-free vitrified human allotransplants. The ultimate impact of these studies will be development of optimized rewarming of vitrified human vascularized composite tissues with reduced risk of cryoprotectant-induced cytotoxicity.