A Multi-thermic Machine Perfusion System Capable of Precise Control of Perfusion Parameters and Stepwise Loading of Cryoprotectants for Muti-scale Organ Preservation

Organ transplantation is the only effective therapeutic modality for end-stage organ diseases. However, short preservation windows (several hours) and donor scarcity limit the development of transplantation. Clinical studies have confirmed that machine perfusion is a more effective approach for organ preservation and repair compared with traditional static cold storage technology. It has been demonstrated that a reduction in temperature can further diminish organ metabolic rates, thus minimizing consumptive injury. Currently, machine perfusion devices for organs above 0 °C are available, but those for sub-zero temperatures and suitable for multiple organs remain underdeveloped. In this study, a multi-thermic machine perfusion (MTMP) system is developed, which enables programmed regulation over a wide temperature range from normothermia, hypothermia to supercooling. The core engineering design incorporates a dual-channel temperature control module, a closed-loop perfusion unit, a pressure feedback unit, and an organ chamber adaptable to diverse organs (1-200 cm3). Our results show that the device is capable of precisely regulating temperature, pressure, and flow rate. We successfully perform perfusion on rat hearts, rabbit kidneys and pig kidneys using the designed MTMP system, achieving stable multi-thermic perfusion preservation. Moreover, stepwise loading of cryoprotective agent is realized by the system, providing a critical pretreatment platform for subsequent organ vitrification. This MTMP system addresses critical gaps in organ preservation technology, offering multi-scale applicability and compatibility with vitrification pretreatment. Its engineering robustness and clinical adaptability lay a foundation for extending preservation duration and accelerating translation to transplant clinics.