SBIR-STTR Award

The technical objective of this Phase 1 proposal is to develop a non-toxic, multi-component, next generation cryostasis cocktail. We seek to develop a unique, holistic and non-toxic approach to bank human organs for several weeks up to a few months. Our approach is based on using the best strategies employed by freeze-tolerant and hibernating animals in nature and then augmenting them with complementary strategies developed through recent scientific understanding, bioengineering principles and modern tools. Our cryopreservation approach is unique from other approaches since we seek to accomplish storage times of several months using an unexplored, yet highly promising methodology. Importantly, our approach will not seek to solve all the problems needed for vitrification or supercooling, but rather will be the first to develop a protocol for organ preservation in a frozen state using high subzero cryogenic storage temperatures (ranging from -5 to -20 C) combined with metabolic depression. This program targets the banking of human livers, but our discoveries and solutions should be translatable to other organ systems as well as to limbs and other VCA, potentially as early as during phase 2 of this project.

This program targets the banking of human organs and tissues for urgent trauma and transplantation medicine as well as for regenerative medicine and tissue manufacturing more broadly. We propose a nature-inspired, holistic and non-toxic solution to dramatically extend preservation times by employing the best strategies used by freeze-tolerant and hibernating animals in Nature augmented with complementary bioengineering and biopreservation principles. Importantly, we dont seek to solve all the problems needed for vitrification or classical cryopreservation, but rather be first to develop organ preservation in a controlled, partially frozen equilibrium state using high subzero temperatures ( -5 to -30 C) - combined with metabolic depression and stress tolerance. An integrated approach is conceived to develop new stasis cocktails optimized for the critical phases of protection (prior to storage), preservation (during storage) and revival-resuscitation (after storage). The storage capability at -20C established in Phase I for hepatocytes will be extended in Phase II through 3 principal efforts: (i) further optimization of the prototype cryostasis cocktail and protocol optimization, (ii) scale-up via our proven whole rat liver models, (iii) initial scaling to preserve human livers and assessment using the Harvard/MGH liver perfusion platform and, as a stretch goal, full human liver pseudo transplants.