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Abstract Preserving organs at subzero temperatures with halted metabolic activity holds the potential to prolong preservation and expand the donor organ pool for transplant. Our group recently introduced partial freezing, a novel approach in high-subzero storage at -15 °C, enabling 5-day storage of rodent livers through precise control over ice nucleation and unfrozen fraction. However, increased vascular resistance and tissue edema suggested a need for improvements to extend viable preservation. Here, we describe an optimized partial freezing protocol with key optimizations, including an increased concentration of polyethylene glycol (PEG) to enhance membrane stability while minimizing shear stress during cryoprotectant unloading with an acclimation period and a maintained osmotic balance through an increase in bovine serum albumin (BSA). These approaches ensured the viability during preservation and recovery processes, promoting liver function and ensuring optimal preservation. This was evidenced by increased oxygen consumption, decreased vascular resistance, and edema. Ultimately, we show that using the optimized protocol, livers can be stored for 10 days with comparable vascular resistance and lactate levels to 5 days, outperforming the viability of time-matched static cold stored (SCS) livers as the current gold standard. This study represents a significant advancement in expanding organ availability through prolonged preservation, thereby revolutionizing transplant medicine.

Organ transplantation remains the only treatment option for patients with end-stage organ failure. The last decade has seen a flurry of activity in improving organ preservation technologies, which promise to increase utilization in a dramatic fashion. They also bring the promise of extending the preservation duration significantly, which opens the doors to sharing organs across local and international boundaries and transforms the field. In this work, we review the recent literature on machine perfusion of livers across various protocols in development and clinical use, in the context of extending the preservation duration. We then review the next generation of technologies that have the potential to further extend the limits and open the door to banking organs, including supercooling, partial freezing, and nanowarming, and outline the opportunities arising in the field for researchers in the short and long term.